Skip to main content

Advertisement

SpringerLink
Log in

Caveolin-1 in tumor progression: the good, the bad and the ugly

  • NON-THEMATIC REVIEW
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Caveolin-1 (Cav1) is a multifunctional scaffolding protein with multiple binding partners that is associated with cell surface caveolae and the regulation of lipid raft domains. Cav1 regulates multiple cancer-associated processes including cellular transformation, tumor growth, cell migration and metastasis, cell death and survival, multidrug resistance and angiogenesis. However, Cav1 has been reported to impact both positively and negatively on various aspects of tumor progression and while reported to function as a tumor suppressor, it has also been identified as a poor prognostic factor in various human cancers. In this review, we survey the functional roles of Cav1 in cancer and argue that Cav1 function is interdependent on tumor stage and the expression of molecular effectors that impact on its role during tumor progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Hanahan, D., & Weinberg, R. A. (2000). The hallmarks of cancer. Cell, 100(1), 57–70.

    PubMed  CAS  Google Scholar 

  2. Yamada, E. (1955). The fine structure of the gall bladder epithelium of the mouse. Journal of Biophysical and Biochemical Cytology, 1(5), 445–458.

    Article  PubMed  CAS  Google Scholar 

  3. Palade, G. E. (1953). Fine structure of blood capillaries. Journal of Applied Physiology, 24, 1424.

    Google Scholar 

  4. Rothberg, K. G., Heuser, J. E., Donzell, W. C., Ying, Y. S., Glenney, J. R., & Anderson, R. G. (1992). Caveolin, a protein component of caveolae membrane coats. Cell, 68(4), 673–82.

    PubMed  CAS  Google Scholar 

  5. Kurzchalia, T. V., Dupree, P., Parton, R. G., Kellner, R., Virta, H., Lehnert, M., et al. (1992). VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles. Journal of Cell Biology, 118(5), 1003–1014.

    PubMed  CAS  Google Scholar 

  6. Glenney Jr., J. R., & Soppet, D. (1992). Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Proceedings of the National Academy of Sciences of the United States of America, 89(21), 10517–10521.

    PubMed  CAS  Google Scholar 

  7. Williams, T. M., & Lisanti, M. P. (2005). Caveolin-1 in oncogenic transformation, cancer, and metastasis. American Journal of Physiology. Cell Physiology, 288(3), C494–506.

    PubMed  CAS  Google Scholar 

  8. Navarro, A., Anand-Apte, B., & Parat, M.-O. (2004). A role for caveolae in cell migration. ASEB Journal, 18(15), 1801–1811.

    CAS  Google Scholar 

  9. Parton, R. G., & Simons, K. (2007). The multiple faces of caveolae. Nature Reviews. Molecular Cell Biology, 8(3), 185–194.

    PubMed  CAS  Google Scholar 

  10. Koleske, A. J., Baltimore, D., & Lisanti, M. P. (1995). Reduction of caveolin and caveolae in oncogenically transformed cells. Proceedings of the National Academy of Sciences of the United States of America, 92(5), 1381–1385.

    PubMed  CAS  Google Scholar 

  11. Capozza, F., Williams, T. M., Schubert, W., McClain, S., Bouzahzah, B., Sotgia, F., et al. (2003). Absence of caveolin-1 sensitizes mouse skin to carcinogen-induced epidermal hyperplasia and tumor formation. American Journal of Pathology, 162(6), 2029–2039.

    PubMed  CAS  Google Scholar 

  12. Lee, S. W., Reimer, C. L., Oh, P., Campbell, D. B., & Schnitzer, J. E. (1998). Tumor cell growth inhibition by caveolin re-expression in human breast cancer cells. Oncogene, 16(11), 1391–1397.

    PubMed  CAS  Google Scholar 

  13. Engelman, J. A., Zhang, X. L., Galbiati, F., & Lisanti, M. P. (1998). Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav-1, -2, and -3). Cav-1 and Cav-2 genes map to a known tumor suppressor locus (6-A2/7q31). FEBS Letters, 429(3), 330–336.

    PubMed  CAS  Google Scholar 

  14. Razani, B., Schlegel, A., Liu, J., & Lisanti, M. P. (2001). Caveolin-1, a putative tumour suppressor gene. Biochemical Society Transactions, 29(Pt 4), 494–499.

    PubMed  CAS  Google Scholar 

  15. Patel, H. H., Murray, F., & Insel, P. A. (2008). Caveolae as organizers of pharmacologically relevant signal transduction molecules. Annual Review of Pharmacology and Toxicology, 48, 359–391.

    PubMed  CAS  Google Scholar 

  16. Hayashi, K., Matsuda, S., Machida, K., Yamamoto, T., Fukuda, Y., Nimura, Y., et al. (2001). Invasion activating caveolin-1 mutation in human scirrhous breast cancers. Cancer Research, 61(6), 2361–2364.

    PubMed  CAS  Google Scholar 

  17. Lajoie, P., Partridge, E., Guay, G., Goetz, J. G., Pawling, J., Lagana, A., et al. (2007). Plasma membrane domain organization regulates EGFR signaling in tumor cells. Journal of Cell Biology, 179(2), 341–56.

    PubMed  CAS  Google Scholar 

  18. Ross, D. T., Scherf, U., Eisen, M. B., Perou, C. M., Rees, C., Spellman, P., et al. (2000). Systematic variation in gene expression patterns in human cancer cell lines. Nature Genetics, 24(3), 227–35.

    PubMed  CAS  Google Scholar 

  19. Liscovitch, M., Burgermeister, E., Jain, N., Ravid, D., Shatz, M., & Tencer, L. (2005). Caveolin and cancer: A complex relationship. In M Mattson (Ed.), Membrane microdomain signaling lipid rafts in biology and medicine (pp. 161–190). Totowa, NJ: Human Press.

    Google Scholar 

  20. Fra, A. M., Williamson, E., Simons, K., & Parton, R. G. (1995). De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proceedings of the National Academy of Sciences of the United States of America, 92(19), 8655–8659.

    PubMed  CAS  Google Scholar 

  21. Williams, T. M., & Lisanti, M. P. (2004). The Caveolin genes: From cell biology to medicine. Annals of Medicine, 36(8), 584–895.

    PubMed  CAS  Google Scholar 

  22. Scherer, P. E., Lewis, R. Y., Volonte, D., Engelman, J. A., Galbiati, F., Couet, J., et al. (1997). Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo. Journal of Biological Chemistry, 272(46), 29337–29346.

    PubMed  CAS  Google Scholar 

  23. Razani, B. (2002). Caveolin-2-deficient mice show evidence of severe pulmonary dysfunction without disruption of caveolae. Molecular and Cellular Biology, 22, 2329–2344.

    PubMed  CAS  Google Scholar 

  24. Lahtinen, U., Honsho, M., Parton, R. G., Simons, K., & Verkade, P. (2003). Involvement of caveolin-2 in caveolar biogenesis in MDCK cells. FEBS Letters, 538(1–3), 85–88.

    PubMed  CAS  Google Scholar 

  25. Way, M., & Parton, R. G. (1995). M-caveolin, a muscle-specific caveolin-related protein. FEBS Letters, 376(1–2), 108–112.

    PubMed  CAS  Google Scholar 

  26. Silva, W. I., Maldonado, H. M., Lisanti, M. P., Devellis, J., Chompre, G., Mayol, N., et al. (1999). Identification of caveolae and caveolin in C6 glioma cells. International Journal of Developmental Neuroscience, 17(7), 705–714.

    PubMed  CAS  Google Scholar 

  27. Galbiati, F., Engelman, J. A., Volonte, D., Zhang, X. L., Minetti, C., Li, M., et al. (2001). Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and t-tubule abnormalities. Journal of Biological Chemistry, 276(24), 21425–21433.

    PubMed  CAS  Google Scholar 

  28. Li, S., Seitz, R., & Lisanti, M. P. (1996). Phosphorylation of caveolin by src tyrosine kinases. The alpha-isoform of caveolin is selectively phosphorylated by v-Src in vivo. Journal of Biological Chemistry, 271(7), 3863–3868.

    PubMed  CAS  Google Scholar 

  29. Glenney Jr., J. R. (1989). Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. Journal of Biological Chemistry, 264(34), 20163–20166.

    PubMed  CAS  Google Scholar 

  30. Sanguinetti, A. R., & Mastick, C. C. (2003). c-Abl is required for oxidative stress-induced phosphorylation of caveolin-1 on tyrosine 14. Cellular Signalling, 15(3), 289–298.

    PubMed  CAS  Google Scholar 

  31. Sanguinetti, A. R., Cao, H., & Corley Mastick, C. (2003). Fyn is required for oxidative- and hyperosmotic-stress-induced tyrosine phosphorylation of caveolin-1. Biochemical Journal, 376(Pt 1), 159–168.

    PubMed  CAS  Google Scholar 

  32. Schlegel, A., Arvan, P., & Lisanti, M. P. (2001). Caveolin-1 binding to endoplasmic reticulum membranes and entry into the regulated secretory pathway are regulated by serine phosphorylation. Protein sorting at the level of the endoplasmic reticulum. Journal of Biological Chemistry, 276(6), 4398–4408.

    PubMed  CAS  Google Scholar 

  33. Dietzen, D. J., Hastings, W. R., & Lublin, D. M. (1995). Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. Journal of Biological Chemistry, 270(12), 6838–6842.

    PubMed  CAS  Google Scholar 

  34. Monier, S., Dietzen, D. J., Hastings, W. R., Lublin, D. M., & Kurzchalia, T. V. (1996). Oligomerization of VIP21-caveolin in vitro is stabilized by long chain fatty acylation or cholesterol. FEBS Letters, 388(2–3), 143–149.

    PubMed  CAS  Google Scholar 

  35. Couet, J., Li, S., Okamoto, T., Ikezu, T., & Lisanti, M. P. (1997). Identification of peptide and protein ligands for the caveolin-scaffolding domain. Implications for the interaction of caveolin with caveolae-associated proteins. Journal of Biological Chemistry, 272(10), 6525–6533.

    PubMed  CAS  Google Scholar 

  36. Garcia-Cardena, G., Martasek, P., Masters, B. S., Skidd, P. M., Couet, J., Li, S., et al. (1997). Dissecting the interaction between nitric oxide synthase (NOS) and caveolin. Functional significance of the nos caveolin binding domain in vivo. Journal of Biological Chemistry, 272(41), 25437–25440.

    PubMed  CAS  Google Scholar 

  37. Li, S., Couet, J., & Lisanti, M. P. (1996). Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases. Journal of Biological Chemistry, 271(46), 29182–29190.

    PubMed  CAS  Google Scholar 

  38. Li, S., Okamoto, T., Chun, M., Sargiacomo, M., Casanova, J. E., Hansen, S. H., et al. (1995). Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. Journal of Biological Chemistry, 270(26), 15693–15701.

    PubMed  CAS  Google Scholar 

  39. Ostrom, R. S., & Insel, P. A. (2004). The evolving role of lipid rafts and caveolae in G protein-coupled receptor signaling: implications for molecular pharmacology. British Journal of Pharmacology, 143(2), 235–245.

    PubMed  CAS  Google Scholar 

  40. Engelman, J. A., Lee, R. J., Karnezis, A., Bearss, D. J., Webster, M., Siegel, P., et al. (1998). Reciprocal regulation of neu tyrosine kinase activity and caveolin-1 protein expression in vitro and in vivo. Implications for human breast cancer. Journal of Biological Chemistry, 273(32), 20448–20455.

    PubMed  CAS  Google Scholar 

  41. Engelman, J. A., Wykoff, C. C., Yasuhara, S., Song, K. S., Okamoto, T., & Lisanti, M. P. (1997). Recombinant expression of caveolin-1 in oncogenically transformed cells abrogates anchorage-independent growth. Journal of Biological Chemistry, 272(26), 16374–16781.

    PubMed  CAS  Google Scholar 

  42. Zhang, X., Ling, M. T., Wang, Q., Lau, C. K., Leung, S. C., Lee, T. K., et al. (2007). Identification of a novel inhibitor of differentiation-1 (ID-1) binding partner, caveolin-1, and its role in epithelial-mesenchymal transition and resistance to apoptosis in prostate cancer cells. Journal of Biological Chemistry, 282(46), 33284–33294.

    PubMed  CAS  Google Scholar 

  43. Bernatchez, P. N., Bauer, P. M., Yu, J., Prendergast, J. S., He, P., & Sessa, W. C. (2005). Dissecting the molecular control of endothelial NO synthase by caveolin-1 using cell-permeable peptides. Proceedings of the National Academy of Sciences of the United States of America, 102(3), 761–766.

    PubMed  CAS  Google Scholar 

  44. Drab, M., Verkade, P., Elger, M., Kasper, M., Lohn, M., Lauterbach, B., et al. (2001). Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science, 293(5539), 2449–2452.

    PubMed  CAS  Google Scholar 

  45. Fernandez, I., Ying, Y., Albanesi, J., & Anderson, R. G. W. (2002). Mechanism of caveolin filament assembly. Proceedings of the National Academy of Sciences of the United States of America, 99(17), 11193–11198.

    PubMed  CAS  Google Scholar 

  46. Monier, S., Parton, R. G., Vogel, F., Behlke, J., Henske, A., & Kurzchalia, T. V. (1995). VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro. Molecular Biology of the Cell, 6(7), 911–927.

    PubMed  CAS  Google Scholar 

  47. Thomsen, P., Roepstorff, K., Stahlhut, M., & van Deurs, B. (2002). Caveolae are highly immobile plasma membrane microdomains, which are not involved in constitutive endocytic trafficking. Molecular Biology of the Cell, 13, 238–250.

    PubMed  CAS  Google Scholar 

  48. Tagawa, A., Mezzacasa, A., Hayer, A., Longatti, A., Pelkmans, L., & Helenius, A. (2005). Assembly and trafficking of caveolar domains in the cell: Caveolae as stable, cargo-triggered, vesicular transporters. Journal of Cell Biology, 170(5), 769–779.

    PubMed  CAS  Google Scholar 

  49. Pol, A., Martin, S., Fernandez, M. A., Ingelmo-Torres, M., Ferguson, C., Enrich, C., et al. (2005). Cholesterol and fatty acids regulate dynamic caveolin trafficking through the golgi complex and between the cell surface and lipid bodies. Molecular Biology of the Cell, 16(4), 2091–2105.

    PubMed  CAS  Google Scholar 

  50. Breuza, L., Corby, S., Arsanto, J. P., Delgrossi, M. H., Scheiffele, P., & Le Bivic, A. (2002). The scaffolding domain of caveolin 2 is responsible for its Golgi localization in Caco-2 cells. Journal of Cell Science, 115(Pt 23), 4457–4467.

    PubMed  CAS  Google Scholar 

  51. Fernandez, M. A. (2006). Caveolin-1 is essential for liver regeneration. Science, 313, 1628–1632.

    PubMed  CAS  Google Scholar 

  52. Drab, M. (2001). Loss of caveolae, vascular dysfunction, and pulmonary defects in Caveolin-1 gene-disrupted mice. Science, 293, 2449–2452.

    PubMed  CAS  Google Scholar 

  53. Schubert, W., Frank, P. G., Razani, B., Park, D. S., Chow, C. W., & Lisanti, M. P. (2001). Caveolae-deficient endothelial cells show defects in the uptake and transport of albumin in vivo. Journal of Biological Chemistry, 276(52), 48619–48622.

    PubMed  CAS  Google Scholar 

  54. Anderson, H. A., Chen, Y., & Norkin, L. C. (1996). Bound simian virus 40 translocates to caveolin-enriched membrane domains, and its entry is inhibited by drugs that selectively disrupt caveolae. Molecular Biology of the Cell, 7(11), 1825–1834.

    PubMed  CAS  Google Scholar 

  55. Pelkmans, L., & Helenius, A. (2002). Endocytosis via caveolae. Traffic, 3(5), 311–320.

    PubMed  CAS  Google Scholar 

  56. Moriyama, T., Marquez, J. P., Wakatsuki, T., & Sorokin, A. (2007). Caveolar endocytosis is critical for BK virus infection of human renal proximal tubular epithelial cells. Journal of Virology, 81(16), 8552–8562.

    PubMed  CAS  Google Scholar 

  57. Schnitzer, J. E., Oh, P., & McIntosh, D. P. (1996). Role of GTP hydrolysis in fission of caveolae directly from plasma membranes [published erratum appears in Science 1996 Nov 15;274(5290):1069]. Science, 274(5285), 239–242.

    PubMed  CAS  Google Scholar 

  58. Minshall, R. D., Tiruppathi, C., Vogel, S. M., Niles, W. D., Gilchrist, A., Hamm, H. E., et al. (2000). Endothelial cell-surface gp60 activates vesicle formation and trafficking via Gi-coupled src kinase signaling pathway. Journal of Cell Biology, 150(5), 1057–1070.

    PubMed  CAS  Google Scholar 

  59. Parton, R. G., Joggerst, B., & Simons, K. (1994). Regulated internalization of caveolae. Journal of Cell Biology, 127, 1199–1215.

    PubMed  CAS  Google Scholar 

  60. Pike, L. J. (2006). Rafts defined: A report on the Keystone symposium on lipid rafts and cell function. Journal of Lipid Research, 47(7), 1597–1598.

    PubMed  CAS  Google Scholar 

  61. Simons, K., & van Meer, G. (1988). Lipid sorting in epithelial cells. Biochemistry, 27(17), 6197–6202.

    PubMed  CAS  Google Scholar 

  62. Brown, D. (1994). GPI-anchored proteins and detergent-resistant membrane domains. Brazilian Journal of Medical and Biological Research, 27(2), 309–315 (Revista brasileira de pesquisas medicas e biologicas/Sociedade Brasileira de Biofisica).

    PubMed  CAS  Google Scholar 

  63. Munro, S. (2003). Lipid rafts: Elusive or illusive? Cell, 115(4), 377–388.

    PubMed  CAS  Google Scholar 

  64. Sharma, P., Varma, R., Sarasij, R. C., Ira, , Gousset, K., Krishnamoorthy, G., et al. (2004). Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell, 116(4), 577–589.

    PubMed  CAS  Google Scholar 

  65. Subczynski, W. K., & Kusumi, A. (2003). Dynamics of raft molecules in the cell and artificial membranes: Approaches by pulse EPR spin labeling and single molecule optical microscopy. Biochimica et Biophysica Acta, 1610(2), 231–243.

    PubMed  CAS  Google Scholar 

  66. Suzuki, K. G., Fujiwara, T. K., Edidin, M., & Kusumi, A. (2007). Dynamic recruitment of phospholipase C gamma at transiently immobilized GPI-anchored receptor clusters induces IP3-Ca2+ signaling: Single-molecule tracking study 2. Journal of Cell Biology, 177(4), 731–742.

    PubMed  CAS  Google Scholar 

  67. Suzuki, K. G., Fujiwara, T. K., Sanematsu, F., Iino, R., Edidin, M., & Kusumi, A. (2007). GPI-anchored receptor clusters transiently recruit Lyn and G alpha for temporary cluster immobilization and Lyn activation: Single-molecule tracking study 1. Journal of Cell Biology, 177(4), 717–730.

    PubMed  CAS  Google Scholar 

  68. Parton, R. G., & Hancock, J. F. (2004). Lipid rafts and plasma membrane microorganization: Insights from Ras. Trends in Cell Biology, 14(3), 141–147.

    PubMed  CAS  Google Scholar 

  69. Murata, M. (1995). VIP21/caveolin is a cholesterol-binding protein. Proceedings of the National Academy of Sciences of the United States of America, 92, 10339–10343.

    PubMed  CAS  Google Scholar 

  70. Fielding, C. J., Bist, A., & Fielding, P. E. (1997). Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers. Proceedings of the National Academy of Sciences of the United States of America, 94(8), 3753–3758.

    PubMed  CAS  Google Scholar 

  71. Nabi, I. R., & Le, P. U. (2003). Caveolae/raft-dependent endocytosis. Journal of Cell Biology, 161(4), 673–677.

    PubMed  CAS  Google Scholar 

  72. Kojic, L., Joshi, B., Lajoie, P., Le, P. U., Leung, S., Cox, M. E., et al. (2007). Raft-dependent endocytosis of autocrine motility factor is phosphatidylinositol-3-kinase-dependent in breast carcinoma cells. Journal of Biological Chemistry, 282(40), 29305–29313.

    PubMed  CAS  Google Scholar 

  73. Le, P. U., Guay, G., Altschuler, Y., & Nabi, I. R. (2002). Caveolin-1 is a negative regulator of caveolae-mediated endocytosis to the endoplasmic reticulum. Journal of Biological Chemistry, 277(5), 3371–3379.

    PubMed  CAS  Google Scholar 

  74. Sharma, D. K., Brown, J. C., Choudhury, A., Peterson, T. E., Holicky, E., Marks, D. L., et al. (2004). Selective stimulation of caveolar endocytosis by glycosphingolipids and cholesterol. Molecular Biology of the Cell, 15(7), 3114–3122.

    PubMed  CAS  Google Scholar 

  75. Hernandez-Deviez, D. J., Howes, M. T., Laval, S. H., Bushby, K., Hancock, J. F., & Parton, R. G. (2007). Caveolin regulates endocytosis of the muscle repair protein, dysferlin. Journal of Biological Chemistry, 283(10), 6476–6488.

    PubMed  Google Scholar 

  76. Hill, M. M., Bastiani, M., Luetterforst, R., Kirkham, M., Kirkham, A., Nixon, S. J., et al. (2008). PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell, 132(1), 113–124.

    PubMed  CAS  Google Scholar 

  77. Liu, L., & Pilch, P. F. (2008). A critical role of cavin (polymerase I and transcript release factor) in caveolae formation and organization. Journal of Biological Chemistry, 283(7), 4314–4322.

    PubMed  CAS  Google Scholar 

  78. Head, B. P., & Insel, P. A. (2007). Do caveolins regulate cells by actions outside of caveolae? Trends in Cell Biology, 17(2), 51–57.

    PubMed  CAS  Google Scholar 

  79. Li, W. P., Liu, P., Pilcher, B. K., & Anderson, R. G. (2001). Cell-specific targeting of caveolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria. Journal of Cell Science, 114(Pt 7), 1397–1408.

    PubMed  CAS  Google Scholar 

  80. Uittenbogaard, A., Ying, Y., & Smart, E. J. (1998). Characterization of a cytosolic heat-shock protein-caveolin chaperone complex. Involvement in cholesterol trafficking. Journal of Biological Chemistry, 273(11), 6525–6532.

    PubMed  CAS  Google Scholar 

  81. Liu, P., Li, W. P., Machleidt, T., & Anderson, R. G. (1999). Identification of caveolin-1 in lipoprotein particles secreted by exocrine cells. Nature Cell Biology, 1(6), 369–375.

    PubMed  CAS  Google Scholar 

  82. Sanna, E., Miotti, S., Mazzi, M., De Santis, G., Canevari, S., & Tomassetti, A. (2007). Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells. Experimental Cell Research, 313(7), 1307–1317.

    PubMed  CAS  Google Scholar 

  83. Feng, Y., Venema, V. J., Venema, R. C., Tsai, N., & Caldwell, R. B. (1999). VEGF induces nuclear translocation of Flk-1/KDR, endothelial nitric oxide synthase, and caveolin-1 in vascular endothelial cells. Biochemical and Biophysical Research Communications, 256(1), 192–197.

    PubMed  CAS  Google Scholar 

  84. Pelkmans, L., Burli, T., Zerial, M., & Helenius, A. (2004). Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell, 118(6), 767–780.

    PubMed  CAS  Google Scholar 

  85. Lee, H., Volonte, D., Galbiati, F., Iyengar, P., Lublin, D. M., Bregman, D. B., et al. (2000). Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette. Molecular Endocrinology, 14(11), 1750–1775.

    PubMed  CAS  Google Scholar 

  86. Beardsley, A., Fang, K., Mertz, H., Castranova, V., Friend, S., & Liu, J. (2005). Loss of Caveolin-1 polarity impedes endothelial cell polarization and directional movement. Journal of Biological Chemistry, 280(5), 3541–3547.

    PubMed  CAS  Google Scholar 

  87. Hill, M. M., Scherbakov, N., Schiefermeier, N., Baran, J., Hancock, J. F., Huber, L.A., et al. (2007). Reassessing the role of phosphocaveolin-1 in cell adhesion and migration. Traffic, 8, 1695–1705.

    PubMed  CAS  Google Scholar 

  88. del Pozo, M. A., Balasubramanian, N., Alderson, N. B., Kiosses, W. B., Grande-Garcia, A., Anderson, R. G., et al. (2005). Phospho-caveolin-1 mediates integrin-regulated membrane domain internalization. Nature Cell Biology, 7(9), 901–908.

    PubMed  CAS  Google Scholar 

  89. Radel, C., & Rizzo, V. (2005). Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization. American Journal of Physiology, Heart and Circulatory Physiology, 288(2), H936–945.

    CAS  Google Scholar 

  90. Wei, Y., Yang, X., Liu, Q., Wilkins, J. A., & Chapman, H. A. (1999). A role for caveolin and the urokinase receptor in integrin-mediated adhesion and signaling. Journal of Cell Biology, 144(6), 1285–1294.

    PubMed  CAS  Google Scholar 

  91. Gaus, K., Le Lay, S., Balasubramanian, N., & Schwartz, M. A. (2006). Integrin-mediated adhesion regulates membrane order. Journal of Cell Biology, 174(5), 725–734.

    PubMed  CAS  Google Scholar 

  92. Goetz, J., Joshi, B., Lajoie, P., Strugnell, S., Scudamore, T., Kojic, L., et al. (2008). Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine phosphorylated caveolin-1. Journal of Cell Biology, 180(6), 1261–1275.

    PubMed  CAS  Google Scholar 

  93. Mettouchi, A., Klein, S., Guo, W., Lopez-Lago, M., Lemichez, E., Westwick, J. K., et al. (2001). Integrin-specific activation of Rac controls progression through the G(1) phase of the cell cycle. Molecular Cell, 8(1), 115–127.

    PubMed  CAS  Google Scholar 

  94. Wary, K. K., Mariotti, A., Zurzolo, C., & Giancotti, F. G. (1998). A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth. Cell, 94(5), 625–634.

    PubMed  CAS  Google Scholar 

  95. Scherer, P. E., Lisanti, M. P., Baldini, G., Sargiacomo, M., Mastick, C. C., & Lodish, H. F. (1994). Induction of caveolin during adipogenesis and association of GLUT4 with caveolin-rich vesicles. Journal of Cell Biology, 127(5), 1233–1243.

    PubMed  CAS  Google Scholar 

  96. Mikol, D. D., Hong, H. L., Cheng, H. L., & Feldman, E. L. (1999). Caveolin-1 expression in Schwann cells. Glia, 27(1), 39–52.

    PubMed  CAS  Google Scholar 

  97. Hagiwara, Y., Nishina, Y., Yorifuji, H., & Kikuchi, T. (2002). Immunolocalization of caveolin-1 and caveolin-3 in monkey skeletal, cardiac and uterine smooth muscles. Cell Structure and Function, 27(5), 375–382.

    PubMed  CAS  Google Scholar 

  98. Kandror, K. V., Stephens, J. M., & Pilch, P. F. (1995). Expression and compartmentalization of caveolin in adipose cells: Coordinate regulation with and structural segregation from GLUT4. Journal of Cell Biology, 129(4), 999–1006.

    PubMed  CAS  Google Scholar 

  99. Campbell, L., Hollins, A. J., Al-Eid, A., Newman, G. R., von Ruhland, C., & Gumbleton, M. (1999). Caveolin-1 expression and caveolae biogenesis during cell transdifferentiation in lung alveolar epithelial primary cultures. Biochemical and Biophysical Research Communications, 262(3), 744–751.

    PubMed  CAS  Google Scholar 

  100. Schwab, W., Galbiati, F., Volonte, D., Hempel, U., Wenzel, K. W., Funk, R. H., et al. (1999). Characterisation of caveolins from cartilage: Expression of caveolin-1, -2 and -3 in chondrocytes and in alginate cell culture of the rat tibia. Histochemistry and Cell Biology, 112(1), 41–49.

    PubMed  CAS  Google Scholar 

  101. Fiucci, G., Ravid, D., Reich, R., & Liscovitch, M. (2002). Caveolin-1 inhibits anchorage-independent growth, anoikis and invasiveness in MCF-7 human breast cancer cells. Oncogene, 21(15), 2365–2375.

    PubMed  CAS  Google Scholar 

  102. Suzuki, T., Suzuki, Y., Hanada, K., Hashimoto, A., Redpath, J. L., Stanbridge, E. J., et al. (1998). Reduction of caveolin-1 expression in tumorigenic human cell hybrids. Journal of Biochemistry (Tokyo), 124(2), 383–388.

    CAS  Google Scholar 

  103. Razani, B., Altschuler, Y., Zhu, L., Pestell, R. G., Mostov, K. E., & Lisanti, M. P. (2000). Caveolin-1 expression is down-regulated in cells transformed by the human papilloma virus in a p53-dependent manner. Replacement of caveolin-1 expression suppresses HPV-mediated cell transformation. Biochemistry, 39(45), 13916–13924.

    PubMed  CAS  Google Scholar 

  104. Park, D. S., Razani, B., Lasorella, A., Schreiber-Agus, N., Pestell, R. G., Iavarone, A., et al. (2001). Evidence that Myc isoforms transcriptionally repress caveolin-1 gene expression via an INR-dependent mechanism. Biochemistry, 40(11), 3354–3362.

    PubMed  CAS  Google Scholar 

  105. Galbiati, F., Volonte, D., Engelman, J. A., Watanabe, G., Burk, R., Pestell, R. G., et al. (1998). Targeted downregulation of caveolin-1 is sufficient to drive cell transformation and hyperactivate the p42/44 MAP kinase cascade. EMBO Journal, 17(22), 6633–6648.

    PubMed  CAS  Google Scholar 

  106. Sasai, K., Kakumoto, K., Hanafusa, H., & Akagi, T. (2007). The Ras-MAPK pathway downregulates caveolin-1 in rodent fibroblast but not in human fibroblasts: Implications in the resistance to oncogene-mediated transformation. Oncogene, 26(3), 449–455.

    PubMed  CAS  Google Scholar 

  107. Tirado, O. M., Mateo-Lozano, S., Villar, J., Dettin, L. E., Llort, A., Gallego, S., et al. (2006). Caveolin-1 (CAV1) is a target of EWS/FLI-1 and a key determinant of the oncogenic phenotype and tumorigenicity of Ewing’s sarcoma cells. Cancer Research, 66(20), 9937–9947.

    PubMed  CAS  Google Scholar 

  108. Cantiani, L., Manara, M. C., Zucchini, C., De Sanctis, P., Zuntini, M., Valvassori, L., et al. (2007). Caveolin-1 reduces osteosarcoma metastases by inhibiting c-Src activity and met signaling. Cancer Research, 67(16), 7675–7685.

    PubMed  CAS  Google Scholar 

  109. Zou, W., McDaneld, L., & Smith, L. M. (2003). Caveolin-1 haploinsufficiency leads to partial transformation of human breast epithelial cells. Anticancer Research, 23(6C), 4581–4586.

    PubMed  CAS  Google Scholar 

  110. Zhang, X., Shen, P., Coleman, M., Zou, W., Loggie, B. W., Smith, L. M., et al. (2005). Caveolin-1 down-regulation activates estrogen receptor alpha expression and leads to 17beta-estradiol-stimulated mammary tumorigenesis. Anticancer Research, 25(1A), 369–375.

    PubMed  Google Scholar 

  111. Williams, T. M., Lee, H., Cheung, M. W., Cohen, A. W., Razani, B., Iyengar, P., et al. (2004). Combined loss of INK4a and caveolin-1 synergistically enhances cell proliferation and oncogene-induced tumorigenesis: Role of INK4a/CAV-1 in mammary epithelial cell hyperplasia. Journal of Biological Chemistry, 279(23), 24745–24756.

    PubMed  CAS  Google Scholar 

  112. Williams, T. M., Cheung, M. W., Park, D. S., Razani, B., Cohen, A. W., Muller, W. J., et al. (2003). Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice. Molecular Biology of the Cell, 14(3), 1027–1042.

    PubMed  CAS  Google Scholar 

  113. Williams, T. M., Medina, F., Badano, I., Hazan, R. B., Hutchinson, J., Muller, W. J., et al. (2004). Caveolin-1 gene disruption promotes mammary tumorigenesis and |dramatically enhances lung metastasis in vivo: Role of cav-1 in cell invasiveness and matrix metalloproteinase (MMP-2/9) secretion. Journal of Biological Chemistry, 279(49), 51630–51646.

    PubMed  CAS  Google Scholar 

  114. Lee, H., Park, D. S., Razani, B., Russell, R. G., Pestell, R. G., & Lisanti, M. P. (2002). Caveolin-1 mutations (P132L and null) and the pathogenesis of breast cancer: Caveolin-1 (P132L) behaves in a dominant-negative manner and caveolin-1 (−/−) null mice show mammary epithelial cell hyperplasia. American Journal of Pathology, 161(4), 1357–1369.

    PubMed  CAS  Google Scholar 

  115. Sotgia, F., Williams, T. M., Schubert, W., Medina, F., Minetti, C., Pestell, R. G., et al. (2006). Caveolin-1 deficiency (−/−) conveys premalignant alterations in mammary epithelia, with abnormal lumen formation, growth factor independence, and cell invasiveness. American Journal of Pathology, 168(1), 292–309.

    PubMed  CAS  Google Scholar 

  116. Sotgia, F., Schubert, W., Pestell, R. G., & Lisanti, M. P. (2006). Genetic ablation of caveolin-1 in mammary epithelial cells increases milk production and hyper-activates STAT5a signaling. Cancer Biology & Therapy, 5(3), 292–297.

    CAS  Google Scholar 

  117. Sloan, E. K., Stanley, K. L., & Anderson, R. L. (2004). Caveolin-1 inhibits breast cancer growth and metastasis. Oncogene, 23(47), 7893–7897.

    PubMed  CAS  Google Scholar 

  118. Hurlstone, A. F., Reid, G., Reeves, J. R., Fraser, J., Strathdee, G., Rahilly, M., et al. (1999). Analysis of the CAVEOLIN-1 gene at human chromosome 7q31.1 in primary tumours and tumour-derived cell lines. Oncogene, 18(10), 1881–1890.

    PubMed  CAS  Google Scholar 

  119. Li, T., Sotgia, F., Vuolo, M. A., Li, M., Yang, W. C., Pestell, R. G., et al. (2006). Caveolin-1 mutations in human breast cancer: functional association with estrogen receptor alpha-positive status. American Journal of Pathology, 168(6), 1998–2013.

    PubMed  CAS  Google Scholar 

  120. Han, S. E., Park, K. H., Lee, G., Huh, Y. J., & Min, B. M. (2004). Mutation and aberrant expression of Caveolin-1 in human oral squamous cell carcinomas and oral cancer cell lines. International Journal of Oncology, 24(2), 435–440.

    PubMed  CAS  Google Scholar 

  121. Haeusler, J., Hoegel, J., Bachmann, N., Herkommer, K., Paiss, T., Vogel, W., et al. (2005). Association of a CAV-1 haplotype to familial aggressive prostate cancer. The Prostate, 65(2), 171–177.

    PubMed  CAS  Google Scholar 

  122. Cui, J., Rohr, L. R., Swanson, G., Speights, V. O., Maxwell, T., & Brothman, A. R. (2001). Hypermethylation of the caveolin-1 gene promoter in prostate cancer. The Prostate, 46(3), 249–256.

    PubMed  CAS  Google Scholar 

  123. Williams, T. M., Hassan, G. S., Li, J., Cohen, A. W., Medina, F., Frank, P. G., et al. (2005). Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: Genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice. Journal of Biological Chemistry, 280(26), 25134–25145.

    PubMed  CAS  Google Scholar 

  124. Nasu, Y., Timme, T. L., Yang, G., Bangma, C. H., Li, L., Ren, C., et al. (1998). Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells. Nature Medicine, 4(9), 1062–1064.

    PubMed  CAS  Google Scholar 

  125. Li, L., Yang, G., Ebara, S., Satoh, T., Nasu, Y., Timme, T. L., et al. (2001). Caveolin-1 mediates testosterone-stimulated survival/clonal growth and promotes metastatic activities in prostate cancer cells. Cancer Research, 61(11), 4386–4392.

    PubMed  CAS  Google Scholar 

  126. Satoh, T., Yang, G., Egawa, S., Addai, J., Frolov, A., Kuwao, S., et al. (2003). Caveolin-1 expression is a predictor of recurrence-free survival in pT2N0 prostate carcinoma diagnosed in Japanese patients. Cancer, 97(5), 1225–1233.

    PubMed  CAS  Google Scholar 

  127. Yang, G., Truong, L. D., Wheeler, T. M., & Thompson, T. C. (1999). Caveolin-1 expression in clinically confined human prostate cancer: A novel prognostic marker. Cancer Research, 59(22), 5719–5723.

    PubMed  CAS  Google Scholar 

  128. Suzuoki, M., Miyamoto, M., Kato, K., Hiraoka, K., Oshikiri, T., Nakakubo, Y., et al. (2002). Impact of caveolin-1 expression on prognosis of pancreatic ductal adenocarcinoma. British Journal of Cancer, 87(10), 1140–1144.

    PubMed  CAS  Google Scholar 

  129. Ando, T., Ishiguro, H., Kimura, M., Mitsui, A., Mori, Y., Sugito, N., et al. (2007). The overexpression of caveolin-1 and caveolin-2 correlates with a poor prognosis and tumor progression in esophageal squamous cell carcinoma. Oncology Reports, 18(3), 601–609.

    PubMed  CAS  Google Scholar 

  130. Kato, K., Hida, Y., Miyamoto, M., Hashida, H., Shinohara, T., Itoh, T., et al. (2002). Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer, 94(4), 929–933.

    PubMed  CAS  Google Scholar 

  131. Joshi, B., Strugnell, S., Goetz, J., Kojic, L., Cox, M., Wiseman, S., et al. (2008). Rho/ROCK signaling acts via phospho-caveolin-1 to regulate focal adhesion dynamics and tumor cell migration. Cancer Research, (in press).

  132. Pinilla, S. M., Honrado, E., Hardisson, D., Benitez, J., & Palacios, J. (2006). Caveolin-1 expression is associated with a basal-like phenotype in sporadic and hereditary breast cancer. Breast Cancer Research and Treatment, 99(1), 85–90.

    PubMed  CAS  Google Scholar 

  133. Savage, K., Lambros, M. B., Robertson, D., Jones, R. L., Jones, C., Mackay, A., et al. (2007). Caveolin 1 is overexpressed and amplified in a subset of basal-like and metaplastic breast carcinomas: A morphologic, ultrastructural, immunohistochemical, and in situ hybridization analysis. Clinical Cancer Research, 13(1), 90–101.

    PubMed  CAS  Google Scholar 

  134. Joo, H. J., Oh, D. K., Kim, Y. S., Lee, K. B., & Kim, S. J. (2004). Increased expression of caveolin-1 and microvessel density correlates with metastasis and poor prognosis in clear cell renal cell carcinoma. BJU International, 93(3), 291–296.

    PubMed  CAS  Google Scholar 

  135. Phuoc, N. B., Ehara, H., Gotoh, T., Nakano, M., Yokoi, S., Deguchi, T., et al. (2007). Immunohistochemical analysis with multiple antibodies in search of prognostic markers for clear cell renal cell carcinoma. Urology, 69(5), 843–848.

    PubMed  Google Scholar 

  136. Campbell, L., Gumbleton, M., & Griffiths, D. F. (2003). Caveolin-1 overexpression predicts poor disease-free survival of patients with clinically confined renal cell carcinoma. British Journal of Cancer, 89(10), 1909–1913.

    PubMed  CAS  Google Scholar 

  137. Barresi, V., Cerasoli, S., Paioli, G., Vitarelli, E., Giuffre, G., Guiducci, G., et al. (2006). Caveolin-1 in meningiomas: Expression and clinico-pathological correlations. Acta Neuropathologica, 112(5), 617–626.

    PubMed  CAS  Google Scholar 

  138. Ho, C. C., Huang, P. H., Huang, H. Y., Chen, Y. H., Yang, P. C., & Hsu, S. M. (2002). Up-regulated caveolin-1 accentuates the metastasis capability of lung adenocarcinoma by inducing filopodia formation. American Journal of Pathology, 161(5), 1647–1656.

    PubMed  CAS  Google Scholar 

  139. Ho, C. C., Kuo, S. H., Huang, P. H., Huang, H. Y., Yang, C. H., & Yang, P. C. (2007). Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy. Lung Cancer, 59(1), 105–110.

    PubMed  Google Scholar 

  140. Moon, K. C., Lee, G. K., Yoo, S. H., Jeon, Y. K., Chung, J. H., Han, J., et al. (2005). Expression of caveolin-1 in pleomorphic carcinoma of the lung is correlated with a poor prognosis. Anticancer Research, 25(6C), 4631–4637.

    PubMed  CAS  Google Scholar 

  141. Yoo, S. H., Park, Y. S., Kim, H. R., Sung, S. W., Kim, J. H., Shim, Y. S., et al. (2003). Expression of caveolin-1 is associated with poor prognosis of patients with squamous cell carcinoma of the lung. Lung Cancer, 42(2), 195–202.

    PubMed  Google Scholar 

  142. Yang, G., Timme, T. L., Frolov, A., Wheeler, T. M., & Thompson, T. C. (2005). Combined c-Myc and caveolin-1 expression in human prostate carcinoma predicts prostate carcinoma progression. Cancer, 103(6), 1186–1194.

    PubMed  CAS  Google Scholar 

  143. Sagara, Y., Mimori, K., Yoshinaga, K., Tanaka, F., Nishida, K., Ohno, S., et al. (2004). Clinical significance of Caveolin-1, Caveolin-2 and HER2/neu mRNA expression in human breast cancer. British Journal of Cancer, 91(5), 959–965.

    PubMed  CAS  Google Scholar 

  144. Sunaga, N., Miyajima, K., Suzuki, M., Sato, M., White, M. A., Ramirez, R. D., et al. (2004). Different roles for caveolin-1 in the development of non-small cell lung cancer versus small cell lung cancer. Cancer Research, 64(12), 4277–4285.

    PubMed  CAS  Google Scholar 

  145. Wikman, H., Seppanen, J. K., Sarhadi, V. K., Kettunen, E., Salmenkivi, K., Kuosma, E., et al. (2004). Caveolins as tumour markers in lung cancer detected by combined use of cDNA and tissue microarrays. The Journal of Pathology, 203(1), 584–593.

    PubMed  CAS  Google Scholar 

  146. Wiechen, K., Diatchenko, L., Agoulnik, A., Scharff, K. M., Schober, H., Arlt, K., et al. (2001). Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene. American Journal of Pathology, 159(5), 1635–1643.

    PubMed  CAS  Google Scholar 

  147. Davidson, B., Nesland, J. M., Goldberg, I., Kopolovic, J., Gotlieb, W. H., Bryne, M., et al. (2001). Caveolin-1 expression in advanced-stage ovarian carcinoma—a clinicopathologic study. Gynecologic Oncology, 81(2), 166–171.

    PubMed  CAS  Google Scholar 

  148. Aldred, M. A., Ginn-Pease, M. E., Morrison, C. D., Popkie, A. P., Gimm, O., Hoang-Vu, C., et al. (2003). Caveolin-1 and caveolin-2, together with three bone morphogenetic protein-related genes, may encode novel tumor suppressors down-regulated in sporadic follicular thyroid carcinogenesis. Cancer Research, 63(11), 2864–2871.

    PubMed  CAS  Google Scholar 

  149. Wiechen, K., Sers, C., Agoulnik, A., Arlt, K., Dietel, M., Schlag, P. M., et al. (2001). Down-regulation of caveolin-1, a candidate tumor suppressor gene, in sarcomas. American Journal of Pathology, 158(3), 833–839.

    PubMed  CAS  Google Scholar 

  150. Forget, M. A., Desrosiers, R. R., Del, M., Moumdjian, R., Shedid, D., Berthelet, F., et al. (2002). The expression of Rho proteins decreases with human brain tumor progression: Potential tumor markers. Clinical & Experimental Metastasis, 19(1), 9–15.

    CAS  Google Scholar 

  151. Cassoni, P., Senetta, R., Castellano, I., Ortolan, E., Bosco, M., Magnani, I., et al. (2007). Caveolin-1 expression is variably displayed in astroglial-derived tumors and absent in oligodendrogliomas: Concrete premises for a new reliable diagnostic marker in gliomas. American Journal of Surgical Pathology, 31(5), 760–769.

    PubMed  Google Scholar 

  152. Bender, F. C., Reymond, M. A., Bron, C., & Quest, A. F. (2000). Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity. Cancer Research, 60(20), 5870–5878.

    PubMed  CAS  Google Scholar 

  153. Fine, S. W., Lisanti, M. P., Galbiati, F., & Li, M. (2001). Elevated expression of caveolin-1 in adenocarcinoma of the colon. American Journal of Clinical Pathology, 115(5), 719–724.

    PubMed  CAS  Google Scholar 

  154. Patlolla, J. M., Swamy, M. V., Raju, J., & Rao, C. V. (2004). Overexpression of caveolin-1 in experimental colon adenocarcinomas and human colon cancer cell lines. Oncology Reports, 11(5), 957–963.

    PubMed  CAS  Google Scholar 

  155. Carrion, R., Morgan, B. E., Tannenbaum, M., Salup, R., & Morgan, M. B. (2003). Caveolin expression in adult renal tumors. Urologic Oncology, 21(3), 191–196.

    PubMed  CAS  Google Scholar 

  156. Hung, K. F., Lin, S. C., Liu, C. J., Chang, C. S., Chang, K. W., & Kao, S. Y. (2003). The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis. Journal of Oral Pathology & Medicine, 32(8), 461–467.

    CAS  Google Scholar 

  157. Pflug, B. R., Reiter, R. E., & Nelson, J. B. (1999). Caveolin expression is decreased following androgen deprivation in human prostate cancer cell lines. The Prostate, 40(4), 269–273.

    PubMed  CAS  Google Scholar 

  158. Van den Eynden, G. G., Van Laere, S. J., Van der Auwera, I., Merajver, S. D., Van Marck, E. A., van Dam, P., et al. (2006). Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer. Breast Cancer Research and Treatment, 95(3), 219–228.

    PubMed  Google Scholar 

  159. Nestl, A., Von Stein, O. D., Zatloukal, K., Thies, W. G., Herrlich, P., Hofmann, M., et al. (2001). Gene expression patterns associated with the metastatic phenotype in rodent and human tumors. Cancer Research, 61(4), 1569–1577.

    PubMed  CAS  Google Scholar 

  160. Zhou, H., Jia, L., Wang, S., Wang, H., Chu, H., Hu, Y., et al. (2006). Divergent expression and roles for caveolin-1 in mouse hepatocarcinoma cell lines with varying invasive ability. Biochemical and Biophysical Research Communications, 345(1), 486–494.

    PubMed  CAS  Google Scholar 

  161. Tahir, S. A., Yang, G., Ebara, S., Timme, T. L., Satoh, T., Li, L., et al. (2001). Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer. Cancer Research, 61(10), 3882–3885.

    PubMed  CAS  Google Scholar 

  162. Tsao, S. C., Su, Y. C., Wang, S. L., & Chai, C. Y. (2007). Use of caveolin-1, thyroid transcription factor-1, and cytokeratins 7 and 20 in discriminating between primary and secondary pulmonary adenocarcinoma from breast or colonic origin. Kaohsiung Journal of Medical Sciences, 23(7), 325–331.

    Article  PubMed  Google Scholar 

  163. Ravid, D., Maor, S., Werner, H., & Liscovitch, M. (2005). Caveolin-1 inhibits cell detachment-induced p53 activation and anoikis by upregulation of insulin-like growth factor-I receptors and signaling. Oncogene, 24(8), 1338–1347.

    PubMed  CAS  Google Scholar 

  164. Belanger, M. M., Roussel, E., & Couet, J. (2003). Up-regulation of caveolin expression by cytotoxic agents in drug-sensitive cancer cells. Anticancer Drugs, 14(4), 281–287.

    PubMed  CAS  Google Scholar 

  165. Ravid, D., Maor, S., Werner, H., & Liscovitch, M. (2006). Caveolin-1 inhibits anoikis and promotes survival signaling in cancer cells. Advances in Enzyme Regulation, 46, 163–175.

    PubMed  CAS  Google Scholar 

  166. Okamoto, T., Schlegel, A., Scherer, P. E., & Lisanti, M. P. (1998). Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. Journal of Biological Chemistry, 273(10), 5419–5422.

    PubMed  CAS  Google Scholar 

  167. Couet, J., Sargiacomo, M., & Lisanti, M. P. (1997). Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. Journal of Biological Chemistry, 272(48), 30429–30438.

    PubMed  CAS  Google Scholar 

  168. Yamamoto, M., Toya, Y., Jensen, R. A., & Ishikawa, Y. (1999). Caveolin is an inhibitor of platelet-derived growth factor receptor signaling. Experimental Cell Research, 247(2), 380–388.

    PubMed  CAS  Google Scholar 

  169. Razani, B., Zhang, X. L., Bitzer, M., von Gersdorff, G., Bottinger, E. P., & Lisanti, M. P. (2001). Caveolin-1 regulates transforming growth factor (TGF)-beta/SMAD signaling through an interaction with the TGF-beta type I receptor. Journal of Biological Chemistry, 276(9), 6727–6738.

    PubMed  CAS  Google Scholar 

  170. Bilderback, T. R., Gazula, V. R., Lisanti, M. P., & Dobrowsky, R. T. (1999). Caveolin interacts with Trk A and p75(NTR) and regulates neurotrophin signaling pathways. Journal of Biological Chemistry, 274(1), 257–263.

    PubMed  CAS  Google Scholar 

  171. Matveev, S. V., & Smart, E. J. (2002). Heterologous desensitization of EGF receptors and PDGF receptors by sequestration in caveolae. American Journal of Physiology. Cell Physiology, 282(4), C935–946.

    PubMed  CAS  Google Scholar 

  172. Di Guglielmo, G. M., Le Roy, C., Goodfellow, A. F., & Wrana, J. L. (2003). Distinct endocytic pathways regulate TGF-beta receptor signalling and turnover. Nature Cell Biology, 5(5), 410–421.

    PubMed  Google Scholar 

  173. Mineo, C., James, G. L., Smart, E. J., & Anderson, R. G. (1996). Localization of epidermal growth factor-stimulated Ras/Raf-1 interaction to caveolae membrane. Journal of Biological Chemistry, 271(20), 11930–11935.

    PubMed  CAS  Google Scholar 

  174. Ringerike, T., Blystad, F. D., Levy, F. O., Madshus, I. H., & Stang, E. (2002). Cholesterol is important in control of EGF receptor kinase activity but EGF receptors are not concentrated in caveolae. Journal of Cell Science, 115(Pt 6), 1331–1340.

    PubMed  CAS  Google Scholar 

  175. Puri, C., Tosoni, D., Comai, R., Rabellino, A., Segat, D., Caneva, F., et al. (2005). Relationships between EGFR signaling-competent and endocytosis-competent membrane microdomains. Molecular Biology of the Cell, 16(6), 2704–2718.

    PubMed  CAS  Google Scholar 

  176. Park, W.-Y., Cho, K.-A., Park, J.-S., Kim, D.-I., & Park, S. C. (2001). Attenuation of EGF signaling in Senescent cells by Caveolin. Annals of the New York Academy of Sciences, 928(1), 79–84.

    Article  PubMed  CAS  Google Scholar 

  177. Sigismund, S., Woelk, T., Puri, C., Maspero, E., Tacchetti, C., Transidico, P., et al. (2005). Clathrin-independent endocytosis of ubiquitinated cargos. Proceedings of the National Academy of Sciences of the United States of America, 102(8), 2760–2765.

    PubMed  CAS  Google Scholar 

  178. Kirkham, M., Fujita, A., Chadda, R., Nixon, S. J., Kurzchalia, T. V., Sharma, D. K., et al. (2005). Ultrastructural identification of uncoated caveolin-independent early endocytic vehicles. Journal of Cell Biology, 168(3), 465–476.

    PubMed  CAS  Google Scholar 

  179. Lajoie, P., & Nabi, I. R. (2007). Regulation of raft-dependent endocytosis. Journal of Cellular and Molecular Medicine, 11(4), 644–653.

    PubMed  CAS  Google Scholar 

  180. Hernandez-Deviez, D. J., Howes, M. T., Laval, S. H., Bushby, K., Hancock, J. F., & Parton, R. G. (2008). Caveolin regulates endocytosis of the muscle repair protein, dysferlin. Journal of Biological Chemistry, 283(10), 6476–6488.

    PubMed  CAS  Google Scholar 

  181. Park, J. S., Park, W. Y., Cho, K. A., Kim, D. I., Jhun, B. H., Kim, S. R., et al. (2001). Down-regulation of amphiphysin-1 is responsible for reduced receptor-mediated endocytosis in the senescent cells. FASEB Journal, 15(9), 1625–1627.

    PubMed  CAS  Google Scholar 

  182. Abulrob, A., Giuseppin, S., Andrade, M. F., McDermid, A., Moreno, M., & Stanimirovic, D. (2004). Interactions of EGFR and caveolin-1 in human glioblastoma cells: Evidence that tyrosine phosphorylation regulates EGFR association with caveolae. Oncogene, 23(41), 6967–6979.

    PubMed  CAS  Google Scholar 

  183. Lu, Z., Ghosh, S., Wang, Z., & Hunter, T. (2003). Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell, 4(6), 499–515.

    PubMed  CAS  Google Scholar 

  184. Kim, Y. N., Dam, P., & Bertics, P. J. (2002). Caveolin-1 phosphorylation in human squamous and epidermoid carcinoma cells: Dependence on ErbB1 expression and Src activation. Experimental Cell Research, 280(1), 134–147.

    PubMed  CAS  Google Scholar 

  185. Kim, Y. N., Wiepz, G. J., Guadarrama, A. G., & Bertics, P. J. (2000). Epidermal growth factor-stimulated tyrosine phosphorylation of caveolin-1. Enhanced caveolin-1 tyrosine phosphorylation following aberrant epidermal growth factor receptor status. Journal of Biological Chemistry, 275(11), 7481–7491.

    PubMed  CAS  Google Scholar 

  186. Zhang, B., Peng, F., Wu, D., Ingram, A. J., Gao, B., & Krepinsky, J. C. (2007). Caveolin-1 phosphorylation is required for stretch-induced EGFR and Akt activation in mesangial cells. Cellular Signalling, 19(8), 1690–1700.

    PubMed  CAS  Google Scholar 

  187. Jiang, L. Q., Feng, X., Zhou, W., Knyazev, P. G., Ullrich, A., & Chen, Z. (2006). Csk-binding protein (Cbp) negatively regulates epidermal growth factor-induced cell transformation by controlling Src activation. Oncogene, 25(40), 5495–5506.

    PubMed  CAS  Google Scholar 

  188. Wang, X. Q., Sun, P., & Paller, A. S. (2002). Ganglioside induces caveolin-1 redistribution and interaction with the epidermal growth factor receptor. Journal of Biological Chemistry, 277(49), 47028–47034.

    PubMed  CAS  Google Scholar 

  189. Olivares-Reyes, J. A., Shah, B. H., Hernandez-Aranda, J., Garcia-Caballero, A., Farshori, M. P., Garcia-Sainz, J. A., et al. (2005). Agonist-induced interactions between angiotensin AT1 and epidermal growth factor receptors. Molecular Pharmacology, 68(2), 356–364.

    PubMed  CAS  Google Scholar 

  190. Ushio-Fukai, M., Hilenski, L., Santanam, N., Becker, P. L., Ma, Y., Griendling, K. K., et al. (2001). Cholesterol depletion inhibits epidermal growth factor receptor transactivation by angiotensin II in vascular smooth muscle cells: Role of cholesterol-rich microdomains and focal adhesions in angiotensin II signaling. Journal of Biological Chemistry, 276(51), 48269–48275.

    PubMed  CAS  Google Scholar 

  191. Yamamoto, M., Toya, Y., Schwencke, C., Lisanti, M. P., Myers Jr., M. G., & Ishikawa, Y. (1998). Caveolin is an activator of insulin receptor signaling. Journal of Biological Chemistry, 273(41), 26962–26968.

    PubMed  CAS  Google Scholar 

  192. Wharton, J., Meshulam, T., Vallega, G., & Pilch, P. (2005). Dissociation of insulin receptor expression and signaling from caveolin-1 expression. Journal of Biological Chemistry, 280(14), 13483–13486.

    PubMed  CAS  Google Scholar 

  193. Oh, Y. S., Cho, K. A., Ryu, S. J., Khil, L. Y., Jun, H. S., Yoon, J. W., et al. (2006). Regulation of insulin response in skeletal muscle cell by caveolin status. Journal of Cellular Biochemistry, 99(3), 747–758.

    PubMed  CAS  Google Scholar 

  194. Lu, X., Kambe, F., Cao, X., Yoshida, T., Ohmori, S., Murakami, K., et al. (2006). DHCR24-knockout embryonic fibroblasts are susceptible to serum withdrawal-induced apoptosis because of dysfunction of caveolae and insulin-Akt-Bad signaling. Endocrinology, 147(6), 3123–3132.

    PubMed  CAS  Google Scholar 

  195. Mastick, C. C., Brady, M. J., & Saltiel, A. R. (1995). Insulin stimulates the tyrosine phosphorylation of caveolin. Journal of Cell Biology, 129(6), 1523–1531.

    PubMed  CAS  Google Scholar 

  196. Mastick, C. C., & Saltiel, A. R. (1997). Insulin-stimulated tyrosine phosphorylation of caveolin is specific for the differentiated adipocyte phenotype in 3T3-L1 cells. Journal of Biological Chemistry, 272(33), 20706–20714.

    PubMed  CAS  Google Scholar 

  197. Kimura, A., Mora, S., Shigematsu, S., Pessin, J. E., & Saltiel, A. R. (2002). The insulin receptor catalyzes the tyrosine phosphorylation of caveolin-1. Journal of Biological Chemistry, 277(33), 30153–30158.

    PubMed  CAS  Google Scholar 

  198. Cao, H., Courchesne, W. E., & Mastick, C. C. (2002). A phosphotyrosine-dependent protein interaction screen reveals a role for phosphorylation of caveolin-1 on tyrosine 14: Recruitment of C-terminal Src kinase. Journal of Biological Chemistry, 277(11), 8771–8774.

    PubMed  CAS  Google Scholar 

  199. Cohen, A. W., Razani, B., Wang, X. B., Combs, T. P., Williams, T. M., Scherer, P. E., et al. (2003). Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue. American Journal of Physiology. Cell Physiology, 285(1), C222–235.

    PubMed  CAS  Google Scholar 

  200. Gustavsson, J., Parpal, S., Karlsson, M., Ramsing, C., Thorn, H., Borg, M., et al. (1999). Localization of the insulin receptor in caveolae of adipocyte plasma membrane. FASEB Journal, 13(14), 1961–1971.

    PubMed  CAS  Google Scholar 

  201. Karlsson, M., Thorn, H., Danielsson, A., Stenkula, K. G., Ost, A., Gustavsson, J., et al. (2004). Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes. Cholesterol depletion blocks insulin signalling for metabolic and mitogenic control. European Journal of Biochemistry, 271(12), 2471–2479.

    PubMed  CAS  Google Scholar 

  202. Souto, R. P., Vallega, G., Wharton, J., Vinten, J., Tranum-Jensen, J., & Pilch, P. F. (2003). Immunopurification and characterization of rat adipocyte caveolae suggest their dissociation from insulin signaling. Journal of Biological Chemistry, 278(20), 18321–18329.

    PubMed  CAS  Google Scholar 

  203. Nystrom, F. H., Chen, H., Cong, L. N., Li, Y., & Quon, M. J. (1999). Caveolin-1 interacts with the insulin receptor and can differentially modulate insulin signaling in transfected Cos-7 cells and rat adipose cells. Molecular Endocrinology, 13(12), 2013–2024.

    PubMed  CAS  Google Scholar 

  204. Kabayama, K., Sato, T., Saito, K., Loberto, N., Prinetti, A., Sonnino, S., et al. (2007). Dissociation of the insulin receptor and caveolin-1 complex by ganglioside GM3 in the state of insulin resistance. Proceedings of the National Academy of Sciences of the United States of America, 104(34), 13678–13683.

    PubMed  CAS  Google Scholar 

  205. Bauer, P. M. (2005). Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 102, 204–209.

    PubMed  CAS  Google Scholar 

  206. Gonzalez, E., Nagiel, A., Lin, A. J., Golan, D. E., & Michel, T. (2004). Small interfering RNA-mediated down-regulation of caveolin-1 differentially modulates signaling pathways in endothelial cells. Journal of Biological Chemistry, 279(39), 40659–40669.

    PubMed  CAS  Google Scholar 

  207. Razani, B., Engelman, J. A., Wang, X. B., Schubert, W., Zhang, X. L., Marks, C. B., et al. (2001). Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. Journal of Biological Chemistry, 276(41), 38121–38138.

    PubMed  CAS  Google Scholar 

  208. Galbiati, F., Volonte, D., Liu, J., Capozza, F., Frank, P. G., Zhu, L., et al. (2001). Caveolin-1 expression negatively regulates cell cycle progression by inducing G(0)/G(1) arrest via a p53/p21(WAF1/Cip1)-dependent mechanism. Molecular Biology of the Cell, 12(8), 2229–2244.

    PubMed  CAS  Google Scholar 

  209. Volonte, D., Zhang, K., Lisanti, M. P., & Galbiati, F. (2002). Expression of caveolin-1 induces premature cellular senescence in primary cultures of murine fibroblasts. Molecular Biology of the Cell, 13(7), 2502–2517.

    PubMed  CAS  Google Scholar 

  210. Cho, K. A., Ryu, S. J., Park, J. S., Jang, I. S., Ahn, J. S., Kim, K. T., et al. (2003). Senescent phenotype can be reversed by reduction of caveolin status. Journal of Biological Chemistry, 278(30), 27789–27795.

    PubMed  CAS  Google Scholar 

  211. Scheel, J., Srinivasan, J., Honnert, U., Henske, A., & Kurzchalia, T. V. (1999). Involvement of caveolin-1 in meiotic cell-cycle progression in Caenorhabditis elegans. Nature Cell Biology, 1(2), 127–129.

    PubMed  CAS  Google Scholar 

  212. Hulit, J., Bash, T., Fu, M., Galbiati, F., Albanese, C., Sage, D. R., et al. (2000). The cyclin D1 gene is transcriptionally repressed by caveolin-1. Journal of Biological Chemistry, 275(28), 21203–21209.

    PubMed  CAS  Google Scholar 

  213. Galbiati, F., Volonte, D., Brown, A. M., Weinstein, D. E., Ben-Ze’ev, A., Pestell, R. G., et al. (2000). Caveolin-1 expression inhibits Wnt/beta-catenin/Lef-1 signaling by recruiting beta-catenin to caveolae membrane domains. Journal of Biological Chemistry, 275(30), 23368–23377.

    PubMed  CAS  Google Scholar 

  214. Liu, P., Ying, Y., & Anderson, R. G. (1997). Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae. Proceedings of the National Academy of Sciences of the United States of America, 94(25), 13666–13670.

    PubMed  CAS  Google Scholar 

  215. Liu, P., Ying, Y., Ko, Y. G., & Anderson, R. G. (1996). Localization of platelet-derived growth factor-stimulated phosphorylation cascade to caveolae. Journal of Biological Chemistry, 271(17), 10299–10303.

    PubMed  CAS  Google Scholar 

  216. Smart, E. J., Ying, Y. S., Mineo, C., & Anderson, R. G. (1995). A detergent-free method for purifying caveolae membrane from tissue culture cells. Proceedings of the National Academy of Sciences of the United States of America, 92(22), 10104–10108.

    PubMed  CAS  Google Scholar 

  217. Zhang, W., Razani, B., Altschuler, Y., Bouzahzah, B., Mostov, K. E., Pestell, R. G., et al. (2000). Caveolin-1 inhibits epidermal growth factor-stimulated lamellipod extension and cell migration in metastatic mammary adenocarcinoma cells (MTLn3). Transformation suppressor effects of adenovirus-mediated gene delivery of caveolin-1. Journal of Biological Chemistry, 275(27), 20717–20725.

    PubMed  CAS  Google Scholar 

  218. Engelman, J. A., Chu, C., Lin, A., Jo, H., Ikezu, T., Okamoto, T., et al. (1998). Caveolin-mediated regulation of signaling along the p42/44 MAP kinase cascade in vivo. A role for the caveolin-scaffolding domain. FEBS Letters, 428(3), 205–211.

    PubMed  CAS  Google Scholar 

  219. Cohen, A. W., Park, D. S., Woodman, S. E., Williams, T. M., Chandra, M., Shirani, J., et al. (2003). Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. American Journal of Physiology. Cell Physiology, 284(2), C457–474.

    PubMed  CAS  Google Scholar 

  220. Engelman, J. A., Zhang, X. L., Razani, B., Pestell, R. G., & Lisanti, M. P. (1999). p42/44 MAP kinase-dependent and –independent signaling pathways regulate caveolin-1 gene expression. Activation of Ras-MAP kinase and protein kinase a signaling cascades transcriptionally down-regulates caveolin-1 promoter activity. Journal of Biological Chemistry, 274(45), 32333–32341.

    PubMed  CAS  Google Scholar 

  221. Liu, P., & Anderson, R. G. (1995). Compartmentalized production of ceramide at the cell surface. Journal of Biological Chemistry, 270(45), 27179–27185.

    PubMed  CAS  Google Scholar 

  222. Bilderback, T. R., Grigsby, R. J., & Dobrowsky, R. T. (1997). Association of p75(NTR) with caveolin and localization of neurotrophin-induced sphingomyelin hydrolysis to caveolae. Journal of Biological Chemistry, 272(16), 10922–10927.

    PubMed  CAS  Google Scholar 

  223. Veldman, R. J., Maestre, N., Aduib, O. M., Medin, J. A., Salvayre, R., & Levade, T. (2001). A neutral sphingomyelinase resides in sphingolipid-enriched microdomains and is inhibited by the caveolin-scaffolding domain: Potential implications in tumour necrosis factor signalling. Biochemical Journal, 355(Pt 3), 859–868.

    PubMed  CAS  Google Scholar 

  224. Ko, Y. G., Lee, J. S., Kang, Y. S., Ahn, J. H., & Seo, J. S. (1999). TNF-alpha-mediated apoptosis is initiated in caveolae-like domains. Journal of Immunology, 162(12), 7217–7223.

    CAS  Google Scholar 

  225. Czarny, M., Liu, J., Oh, P., & Schnitzer, J. E. (2003). Transient mechanoactivation of neutral sphingomyelinase in caveolae to generate ceramide. Journal of Biological Chemistry, 278(7), 4424–4430.

    PubMed  CAS  Google Scholar 

  226. Czarny, M., & Schnitzer, J. E. (2004). Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium. American Journal of Physiology Heart and Circulatory Physiology, 287(3), H1344–1352.

    PubMed  CAS  Google Scholar 

  227. Zundel, W., Swiersz, L. M., & Giaccia, A. (2000). Caveolin 1-mediated regulation of receptor tyrosine kinase-associated phosphatidylinositol 3-kinase activity by ceramide. Molecular and Cellular Biology, 20(5), 1507–1514.

    PubMed  CAS  Google Scholar 

  228. Zhuang, L., Kim, J., Adam, R. M., Solomon, K. R., & Freeman, M. R. (2005). Cholesterol targeting alters lipid raft composition and cell survival in prostate cancer cells and xenografts. Journal of Clinical Investigation, 115(4), 959–968.

    PubMed  CAS  Google Scholar 

  229. Liu, J., Lee, P., Galbiati, F., Kitsis, R. N., & Lisanti, M. P. (2001). Caveolin-1 expression sensitizes fibroblastic and epithelial cells to apoptotic stimulation. American Journal of Physiology. Cell Physiology, 280(4), C823–835.

    PubMed  CAS  Google Scholar 

  230. Shack, S., Wang, X. T., Kokkonen, G. C., Gorospe, M., Longo, D. L., & Holbrook, N. J. (2003). Caveolin-induced activation of the phosphatidylinositol 3-kinase/Akt pathway increases arsenite cytotoxicity. Molecular and Cellular Biology, 23(7), 2407–2414.

    PubMed  CAS  Google Scholar 

  231. Lin, M. I., Yu, J., Murata, T., & Sessa, W. C. (2007). Caveolin-1-deficient mice have increased tumor microvascular permeability, angiogenesis, and growth. Cancer Research, 67(6), 2849–2856.

    PubMed  CAS  Google Scholar 

  232. Shajahan, A. N., Wang, A., Decker, M., Minshall, R. D., Liu, M. C., & Clarke, R. (2007). Caveolin-1 tyrosine phosphorylation enhances paclitaxel-mediated cytotoxicity. Journal of Biological Chemistry, 282(8), 5934–5943.

    PubMed  CAS  Google Scholar 

  233. Podar, K., Tai, Y. T., Cole, C. E., Hideshima, T., Sattler, M., Hamblin, A., et al. (2003). Essential role of caveolae in interleukin-6- and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells. Journal of Biological Chemistry, 278(8), 5794–5801.

    PubMed  CAS  Google Scholar 

  234. Li, L., Ren, C. H., Tahir, S. A., Ren, C., & Thompson, T. C. (2003). Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Molecular and Cellular Biology, 23(24), 9389–9404.

    PubMed  CAS  Google Scholar 

  235. Ayala, G. E., Dai, H., Tahir, S. A., Li, R., Timme, T., Ittmann, M., et al. (2006). Stromal antiapoptotic paracrine loop in perineural invasion of prostatic carcinoma. Cancer Research, 66(10), 5159–5164.

    PubMed  CAS  Google Scholar 

  236. Timme, T. L., Goltsov, A., Tahir, S., Li, L., Wang, J., Ren, C., et al. (2000). Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis. Oncogene, 19(29), 3256–3265.

    PubMed  CAS  Google Scholar 

  237. Glait, C., Tencer, L., Ravid, D., Sarfstein, R., Liscovitch, M., & Werner, H. (2006). Caveolin-1 up-regulates IGF-I receptor gene transcription in breast cancer cells via Sp1- and p53-dependent pathways. Experimental Cell Research, 312(19), 3899–3908.

    PubMed  CAS  Google Scholar 

  238. Shaul, P. W., & Anderson, R. G. (1998). Role of plasmalemmal caveolae in signal transduction. American Journal of Physiology, 275(5 Pt 1), L843–851.

    PubMed  CAS  Google Scholar 

  239. Isshiki, M., Ando, J., Korenaga, R., Kogo, H., Fujimoto, T., Fujita, T., et al. (1998). Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges. Proceedings of the National Academy of Sciences of the United States of America, 95(9), 5009–5014.

    PubMed  CAS  Google Scholar 

  240. Isshiki, M., Ando, J., Yamamoto, K., Fujita, T., Ying, Y., & Anderson, R. G. (2002). Sites of Ca(2+) wave initiation move with caveolae to the trailing edge of migrating cells. Journal of Cell Science, 115(Pt 3), 475–484.

    PubMed  CAS  Google Scholar 

  241. Parat, M. O., Anand-Apte, B., & Fox, P. L. (2003). Differential caveolin-1 polarization in endothelial cells during migration in two and three dimensions. Molecular Biology of the Cell, 14(8), 3156–3168.

    PubMed  CAS  Google Scholar 

  242. Lentini, D., Guzzi, F., Pimpinelli, F., Zaninetti, R., Cassetti, A., Coco, S., et al. (2007). Polarization of caveolins and caveolae during migration of immortalized neurons. Journal of Neurochemistry, 104(2), 514–523.

    Google Scholar 

  243. Santilman, V., Baran, J., Anand-Apte, B., Evans, R. M., & Parat, M. O. (2007). Caveolin-1 polarization in transmigrating endothelial cells requires binding to intermediate filaments. Angiogenesis, 10(4), 297–305.

    PubMed  CAS  Google Scholar 

  244. Sun, X. H., Flynn, D. C., Castranova, V., Millecchia, L. L., Beardsley, A. R., & Liu, J. (2007). Identification of a novel domain at the N terminus of caveolin-1 that controls rear polarization of the protein and caveolae formation. Journal of Biological Chemistry, 282(10), 7232–7241.

    PubMed  CAS  Google Scholar 

  245. Zaidel-Bar, R., Itzkovitz, S., Ma’ayan, A., Iyengar, R., & Geiger, B. (2007). Functional atlas of the integrin adhesome. Nature Cell Biology, 9(8), 858–867.

    PubMed  CAS  Google Scholar 

  246. Radel, C., Carlile-Klusacek, M., & Rizzo, V. (2007). Participation of caveolae in beta1 integrin-mediated mechanotransduction. Biochemical and Biophysical Research Communications, 358(2), 626–631.

    PubMed  CAS  Google Scholar 

  247. Cordes, N., Frick, S., Brunner, T. B., Pilarsky, C., Grutzmann, R., Sipos, B., et al. (2007). Human pancreatic tumor cells are sensitized to ionizing radiation by knockdown of caveolin-1. Oncogene, 26(48), 6851–6862.

    PubMed  CAS  Google Scholar 

  248. Swaney, J. S., Patel, H. H., Yokoyama, U., Head, B. P., Roth, D. M., & Insel, P. A. (2006). Focal adhesions in (myo)fibroblasts scaffold adenylyl cyclase with phosphorylated caveolin. Journal of Biological Chemistry, 281(25), 17173–17179.

    PubMed  CAS  Google Scholar 

  249. Grande-Garcia, A., Echarri, A., de Rooij, J., Alderson, N. B., Waterman-Storer, C. M., Valdivielso, J. M., et al. (2007). Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases. Journal of Cell Biology, 177(4), 683–694.

    PubMed  CAS  Google Scholar 

  250. Ikeda, S., Ushio-Fukai, M., Zuo, L., Tojo, T., Dikalov, S., Patrushev, N. A., et al. (2005). Novel role of ARF6 in vascular endothelial growth factor-induced signaling and angiogenesis. Circulation Research, 96(4), 467–475.

    PubMed  CAS  Google Scholar 

  251. Podar, K., Shringarpure, R., Tai, Y. T., Simoncini, M., Sattler, M., Ishitsuka, K., et al. (2004). Caveolin-1 is required for vascular endothelial growth factor-triggered multiple myeloma cell migration and is targeted by bortezomib. Cancer Research, 64(20), 7500–7506.

    PubMed  CAS  Google Scholar 

  252. Bailey, K. M., & Liu, J. (2008). Caveolin-1 up-regulation during epithelial to mesenchymal transition is mediated by focal adhesion kinase. Journal of Biological Chemistry, M709329200.

  253. Lin, M., DiVito, M. M., Merajver, S. D., Boyanapalli, M., & van Golen, K. L. (2005). Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and caveolin-1. Molecular Cancer, 4(1), 21.

    PubMed  Google Scholar 

  254. Orlichenko, L., Huang, B., Krueger, E., & McNiven, M. A. (2006). Epithelial growth factor-induced phosphorylation of caveolin 1 at tyrosine 14 stimulates caveolae formation in epithelial cells. Journal of Biological Chemistry, 281(8), 4570–4579.

    PubMed  CAS  Google Scholar 

  255. Aoki, T., Nomura, R., & Fujimoto, T. (1999). Tyrosine phosphorylation of caveolin-1 in the endothelium. Experimental Cell Research, 253(2), 629–636.

    PubMed  CAS  Google Scholar 

  256. del Pozo, M. A., Alderson, N. B., Kiosses, W. B., Chiang, H. H., Anderson, R. G., & Schwartz, M. A. (2004). Integrins regulate Rac targeting by internalization of membrane domains. Science, 303(5659), 839–842.

    PubMed  CAS  Google Scholar 

  257. Del Pozo, M. A., & Schwartz, M. A. (2007). Rac, membrane heterogeneity, caveolin and regulation of growth by integrins. Trends in Cell Biology, 17(5), 246–250.

    PubMed  CAS  Google Scholar 

  258. Demetriou, M., Granovsky, M., Quaggin, S., & Dennis, J. W. (2001). Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature, 409(6821), 733–739.

    PubMed  CAS  Google Scholar 

  259. Partridge, E. A., Le Roy, C., Di Guglielmo, G. M., Pawling, J., Cheung, P., Granovsky, M., et al. (2004). Regulation of cytokine receptors by Golgi N-glycan processing and endocytosis. Science, 306(5693), 120–124.

    PubMed  CAS  Google Scholar 

  260. Lau, K. S., Partridge, E. A., Grigorian, A., Silvescu, C. I., Reinhold, V. N., Demetriou, M., et al. (2007). Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell, 129(1), 123–134.

    PubMed  CAS  Google Scholar 

  261. Dennis, J. W., Pawling, J., Cheung, P., Partridge, E., & Demetriou, M. (2002). UDP-N-acetylglucosamine:alpha-6-D-mannoside beta1,6 N-acetylglucosaminyltransferase V (Mgat5) deficient mice. Biochimica et Biophysica Acta, 1573(3), 414–422.

    PubMed  CAS  Google Scholar 

  262. Takenaka, Y., Fukumori, T., & Raz, A. (2004). Galectin-3 and metastasis. Glycoconjugate Journal, 19(7–9), 543–549.

    PubMed  Google Scholar 

  263. Nangia-Makker, P., Hogan, V., Honjo, Y., Baccarini, S., Tait, L., Bresalier, R., et al. (2002). Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus Pectin. Journal of the National Cancer Institute, 94(24), 1854–1862.

    PubMed  CAS  Google Scholar 

  264. Pienta, K. J., Naik, H., Akhtar, A., Yamazaki, K., Replogle, T. S., Lehr, J., et al. (1995). Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. Journal of the National Cancer Institute, 87(5), 348–353.

    PubMed  CAS  Google Scholar 

  265. Dewever, J., Frerart, F., Bouzin, C., Baudelet, C., Ansiaux, R., Sonveaux, P., et al. (2007). Caveolin-1 is critical for the maturation of tumor blood vessels through the regulation of both endothelial tube formation and mural cell recruitment. American Journal of Pathology, 171(5), 1619–1628.

    PubMed  CAS  Google Scholar 

  266. Yang, G., Addai, J., Wheeler, T. M., Frolov, A., Miles, B. J., Kadmon, D., et al. (2007). Correlative evidence that prostate cancer cell-derived caveolin-1 mediates angiogenesis. Human Pathology, 38(11), 1688–1695.

    PubMed  CAS  Google Scholar 

  267. Bartz, R., Zhou, J., Hsieh, J. T., Ying, Y., Li, W., & Liu, P. (2007). Caveolin-1 secreting LNCaP cells induce tumor growth of caveolin-1 negative LNCaP cells in vivo. International Journal of Cancer, 122(3), 520–525.

    Google Scholar 

  268. Brouet, A., DeWever, J., Martinive, P., Havaux, X., Bouzin, C., Sonveaux, P., et al. (2005). Antitumor effects of in vivo caveolin gene delivery are associated with the inhibition of the proangiogenic and vasodilatory effects of nitric oxide. FASEB Journal, 19(6), 602–604.

    PubMed  CAS  Google Scholar 

  269. Oh, P., Borgstrom, P., Witkiewicz, H., Li, Y., Borgstrom, B. J., Chrastina, A., et al. (2007). Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung. Nature Biotechnology, 25(3), 327–337.

    PubMed  CAS  Google Scholar 

  270. Oh, P., Li, Y., Yu, J., Durr, E., Krasinska, K. M., Carver, L. A., et al. (2004). Subtractive proteomic mapping of the endothelial surface in lung and solid tumours for tissue-specific therapy. Nature, 429(6992), 629–635.

    PubMed  CAS  Google Scholar 

  271. Gratton, J. P., Lin, M. I., Yu, J., Weiss, E. D., Jiang, Z. L., Fairchild, T. A., et al. (2003). Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice. Cancer Cell, 4(1), 31–39.

    PubMed  CAS  Google Scholar 

  272. Podar, K., & Anderson, K. C. (2006). Caveolin-1 as a potential new therapeutic target in multiple myeloma. Cancer Letters, 233(1), 10–15.

    PubMed  CAS  Google Scholar 

  273. Pramudji, C., Shimura, S., Ebara, S., Yang, G., Wang, J., Ren, C., et al. (2001). In situ prostate cancer gene therapy using a novel adenoviral vector regulated by the caveolin-1 promoter. Clinical Cancer Research, 7(12), 4272–4279.

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Jacky G. Goetz

    Present address: Integrin Signalling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernandez Almagro, 3, 28029, Madrid, Spain

  2. Patrick Lajoie

    Present address: Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

Authors and Affiliations

  1. Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada, V6T1Z3

    Jacky G. Goetz, Patrick Lajoie & Ivan R. Nabi

  2. Department of Surgery, St. Paul’s Hospital and the University of British Columbia, C303 1081 Burrard St., Vancouver, BC, Canada, V6Z1Y6

    Sam M. Wiseman

Authors
  1. Jacky G. Goetz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Lajoie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sam M. Wiseman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivan R. Nabi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ivan R. Nabi.

Additional information

Goetz and Lajoie contributed equally to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goetz, J.G., Lajoie, P., Wiseman, S.M. et al. Caveolin-1 in tumor progression: the good, the bad and the ugly. Cancer Metastasis Rev 27, 715–735 (2008). https://doi.org/10.1007/s10555-008-9160-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-008-9160-9

Keywords

Search

Navigation