Revisiting the role of autophagy in melanoma.

Although alterations of the macroautophagy/autophagy-lysosome pathway have been observed in cancer for many years, the mechanisms underlying these changes and the importance of autophagic and lysosomal reprogramming by cancer have yet to be well identified. Our recent study demonstrates that oncogenic BRAF signaling promotes melanoma growth and resistance to BRAF-targeted therapy through phosphorylation and functional inactivation of TFEB (transcription factor EB) and consequent suppression of the autophagy-lysosome gene network. This is by no means the first time that this pathway has been directly linked to oncogenic BRAF-driven melanoma. The key observations revealed in this study also leads to a complex but growing convergence of our understanding of the biology of the autophagy-lysosome pathway and the mechanisms underlying cancer prevention and treatment.