Aberrant SIRT6 expression contributes to melanoma growth: Role of the autophagy paradox and IGF-AKT signaling

ABSTRACTMelanoma is among the most life-threatening cancers. The pathogenesis of melanoma has not been fully elucidated. Recently, dysregulated macroautophagy/autophagy has been found to play a critical but inconsistent role in modulating melanoma growth at different stages, with the regulatory mechanism unclear. The histone deacetylase SIRT6 (sirtuin 6) is a known autophagy regulator, and its involvement in cancer development has been reported. Therefore, we sought to determine the role of SIRT6 in melanoma growth and detect its possible link with autophagy in the current study. We initially observed that the expression of SIRT6 decreased in primary melanoma but increased in metastatic melanoma compared with melanocytic nevus. Notably, the expression of SIRT6 was significantly correlated with the expression of autophagy biomarkers including MAP1LC3/LC3 and SQSTM1/p62. Furthermore, SIRT6 suppressed the growth of primary melanoma but promoted metastatic melanoma development in an autophagy-dependent way in...