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  • Original Paper
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Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells

Oncogene volume 24, pages 1309–1319 (2005)Cite this article

Abstract

WAVEs (WASP-family verprolin-homologous proteins) regulate the actin cytoskeleton through activation of Arp2/3 complex. As cell motility is regulated by actin cytoskeleton rearrangement and is required for tumor invasion and metastasis, blocking actin polymerization may be an effective strategy to prevent tumor dissemination. We show that WAVEs, especially WAVE2, are essential for invasion and metastasis of melanoma cells. Malignant B16F10 mouse melanoma cells expressed more WAVE1 and WAVE2 proteins and showed higher Rac activity than B16 parental cells, which are neither invasive nor metastatic. The effect of WAVE2 silencing by RNA interference (RNAi) on the highly invasive nature of B16F10 cells was more dramatic than that of WAVE1 RNAi. Membrane ruffling, cell motility, invasion into the extracellular matrix, and pulmonary metastasis of B16F10 cells were suppressed by WAVE2 RNAi. WAVE2 RNAi also had a profound effect on invasion induced by a constitutively active form of Rac (RacCA). In addition, ectopic expression of both RacCA and WAVE2 in B16 cells resulted in further increase in the invasiveness than that observed in B16 cells expressing only RacCA. Thus, WAVE2 acts as the primary effector downstream of Rac to achieve invasion and metastasis, suggesting that suppression of WAVE2 activity holds a promise for preventing cancer invasion and metastasis.

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Acknowledgements

We thank members of the laboratory for help and advice throughout this study, Dr T Azuma for providing the anti-Rac1 antibody, and Dr H Nakagawa for GFP-tagged WAVE1 and WAVE2 constructs. The work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, and Technology of Japan and from the Japan Science and Technology Corporation (JST).

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Authors and Affiliations

  1. Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Shusaku Kurisu, Shiro Suetsugu, Daisuke Yamazaki & Tadaomi Takenawa

  2. Division of Cancer Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Hideki Yamaguchi

  3. CREST, Japan Science and Technology Corp., Tokyo, 108-8639, Japan

    Shusaku Kurisu, Shiro Suetsugu, Daisuke Yamazaki & Tadaomi Takenawa

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  1. Shusaku Kurisu
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Correspondence to Tadaomi Takenawa.

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Kurisu, S., Suetsugu, S., Yamazaki, D. et al. Rac-WAVE2 signaling is involved in the invasive and metastatic phenotypes of murine melanoma cells. Oncogene 24, 1309–1319 (2005). https://doi.org/10.1038/sj.onc.1208177

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