Grant: Travel Awards - Institute Community Support

The E3 ubiquitin ligase Fbw7 (F-box and WD repeat domain-containing 7) is broadly considered as a tumor suppressor because of its role in turnover of several well-known onco-proteins. However, the role of Fbw7 in melanomagenesis is not clear. To investigate the expression profile and biological functions of Fbw7 in melanoma, we examined Fbw7 expression level using melanoma tissue microarray and immunohistochemistry. Our data showed that Fbw7 expression is significantly reduced in primary melanoma compared with dysplastic nevi (P = 0.020) and further reduced in metastatic melanoma compared with primary melanoma (P = 0.011). Furthermore, we observed a strong correlation between negative Fbw7 expression and a worse 5-year survival of melanoma patients (P = 0.015). We also found that both Fbw7 protein and mRNA expression was significantly reduced in 9 melanoma cell lines compared with normal melanocytes. Moreover, our in vitro studies showed a remarkable increase of cell migration and stress fibre formation in Fbw7 knockdown cells, and treatment of selective MEK inhibitor abrogated Fbw7 alpha knockdown induced melanoma cell migration. Taken together, our findings indicate that Fbw7 plays an important role in melanoma progression, and Fbw7 inhibits melanoma cell migration through MAPK-ERK signalling pathway and may serve as a prognostic marker.