Abstract
The human gene Hugl-1 (Llgl/Lgl1) has significant homology to the Drosophila tumor suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that is involved in maintaining cell polarity and epithelial integrity. We speculate that Hugl-1 might play a role in epithelial–mesenchymal transition (EMT) and that loss of Hugl-1 expression plays a role in the development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of Hugl-1 transcription. We found that Hugl-1 was downregulated or lost in all cell lines and in most of the tumor samples analysed, and that these losses were associated with advanced stage of the disease. Reduced Hugl-1 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription–polymerase chain reaction (RT–PCR) analysis. Functional assays with stable Hugl-1-transfected cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Further, downregulation of MMP2 and MMP14 (MT1-MMP) and re-expression of E-cadherin was found in the Hugl-1-expressing cell clones supporting a role of Hugl-1 in EMT. Our studies thus indicate that loss of Hugl-1 expression contributes to melanoma progression.
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Abbreviations
- bp:
-
base pair
- Hugl :
-
human giant larvae
- lgl :
-
lethal giant larvae
- PCR:
-
polymerase chain reaction
- RT:
-
reverse transcription
- EMT:
-
epithelial–mesenchymal transition
- MMP:
-
matrix metalloproteinase
- NHEM:
-
normal human epidermal melanocytes
- NDP:
-
nucleoside diphosphate kinase
- IHC:
-
immunohistochemistry
- PKC:
-
protein kinase C
- Par 6:
-
protease-activated receptor 6
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Acknowledgements
We are indebted to Dr J Johnson (University of Munich, Germany) for providing melanoma cell lines and to Sibylla Lodermeier for excellent technical assistance. This work was supported by grants from the DFG and the Deutsche Krebshilfe to AB.
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Kuphal, S., Wallner, S., Schimanski, C. et al. Expression of Hugl-1 is strongly reduced in malignant melanoma. Oncogene 25, 103–110 (2006). https://doi.org/10.1038/sj.onc.1209008
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DOI: https://doi.org/10.1038/sj.onc.1209008
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