C-myc overexpression drives melanoma metastasis by promoting vasculogenic mimicry via c-myc/snail/Bax signaling

C-myc is a well-characterized proto-oncogene that induces cellular transformation and modulates programmed cell death. while recent studies have demonstrated high expression of c-myc protein in advanced and metastatic melanoma, the clinical and biological implications remain to be fully elucidated. in this study, we investigated the effect of c-myc overexpression in melanoma tumorigenesis. clinicopathological analysis demonstrated that c-myc expression positively correlated with the formation of vasculogenic mimicry (vm) and linearly patterned programmed cell necrosis (lppcn). clinically, high c-myc expression was significantly associated with distant metastasis and poor prognosis, while biologically, c-myc overexpression led to significant increases in cell motility, invasiveness and metastasis. moreover, c-myc induced the formation of vm and promoted the expression of epithelial-mesenchymal transition (emt)-associated protein snail both in vivo and in vitro. high expression of c-myc increased bax expression in hypoxic conditions and induced cell apoptosis. taken together, we conclude that c-myc overexpression promotes the formation of vm by emt and lppcn in melanoma. our improved understanding of the clinical and biological effects of c-myc overexpression in melanoma highlights the incomplete understanding of this oncogene, and indicates that c-myc is a potential therapeutic target of this disease.