REG[gamma] accelerates melanoma formation by regulating Wnt/[beta]-catenin signalling pathway

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