Hepatocyte growth factor (HGF)/ mesenchymal-epithelial transition factor (c-MET) signaling is involved in complex cellular programs that are important for embryonic development and tissue regeneration, but its activity is also utilized by cancer cells during tumor progression.,HGF and c-MET usually mediate heterotypic cell-cell interactions, such as epithelial-mesenchymal, including tumor-stroma interactions.,In the skin, dermal fibroblasts are the main source of HGF.,The presence of c-MET on keratinocytes is crucial for wound healing in the skin.,HGF is not released by normal melanocytes, but as melanocytes express c-MET, they are receptive to HGF, which protects them from apoptosis and stimulates their proliferation and motility.,Dissimilar to melanocytes, melanoma cells not only express c-MET, but also release HGF, thus activating c-MET in an autocrine manner.,Stimulation of the HGF/c-MET pathways contributes to several processes that are crucial for melanoma development, such as proliferation, survival, motility, and invasiveness, including distant metastatic niche formation.,HGF might be a factor in the innate and acquired resistance of melanoma to oncoprotein-targeted drugs.,It is not entirely clear whether elevated serum HGF level is associated with low progression-free survival and overall survival after treatment with targeted therapies.,This review focuses on the role of HGF/c-MET signaling in melanoma with some introductory information on its function in skin and melanocytes.
Melanoma is highly metastatic, and understanding of its molecular mechanism is urgently needed for the development of therapeutic targets and prognostic assessment for metastatic melanoma.,SIRT1 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, belonging to the mammalian sirtuin family.,It has been reported that SIRT1 is associated with metastasis in various cancers.,However, the molecular mechanism of SIRT1 in melanoma metastasis remains to be clarified.,Here we report that SIRT1 induces the epithelial-mesenchymal transition (EMT) by accelerating E-cadherin degradation via autophagy and facilitates melanoma metastasis.,Initially, we found that SIRT1 expression was frequently elevated in metastatic melanoma compared with primary melanoma.,In addition, SIRT1 induced the EMT and promoted cell migration and invasion by decreasing E-cadherin expression.,Further work demonstrated that SIRT1 accelerated the autophagic degradation of E-cadherin through deacetylation of Beclin 1.,In addition, inhibition of autophagy recovered E-cadherin expression and suppressed cell migration and invasion by delaying the degradation of E-cadherin in SIRT1-overexpressing cells.,Overall, our findings reveal a novel molecular mechanism for SIRT1 in melanoma metastasis, indicating that SIRT1 may serve as a viable therapeutic target for metastatic melanoma.