REGγ accelerates melanoma formation by regulating Wnt/β-catenin signalling pathway.

It has been reported that the proteasome activator REG is associated with multiple oncogenic pathways in human cancers. However, the role of REG in the development of melanoma and the underlying mechanisms remain unclear. In this study, we attempted to investigate the effects of REG on human melanoma cell proliferation in vitro and in vivo. We demonstrated that knockdown of REG inhibited melanoma cell growth and arrested melanoma cell at G1 phase. Furthermore, depletion of REG also inhibited the xenograft growth of human melanoma. Mechanistically, REG activates Wnt/-catenin signal pathway by degrading GSK-3 in melanoma cell lines and mouse models. Transient knockdown of -catenin effectively blocked cell proliferation in REG wild-type melanoma cells. In human melanoma samples, REG was overexpressed and positively correlated with -catenin levels. This study demonstrates that REG is a central molecule in the development of melanoma by regulating Wnt/-catenin pathway. This suggests that targeting REG could be an alternative therapeutic approach for melanoma.