Research ArticleCancer

Down-Regulation of Autophagy-Related Protein 5 (ATG5) Contributes to the Pathogenesis of Early-Stage Cutaneous Melanoma

Science Translational Medicine  11 Sep 2013:
Vol. 5, Issue 202, pp. 202ra123
DOI: 10.1126/scitranslmed.3005864

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Getting Melanoma to Eat Itself

Autophagy, which literally means “self-eating,” is a normal cellular process that allows cells to get rid of unnecessary debris and may help them survive under conditions of stress. Autophagy is thought to be dysregulated in tumor cells, but its exact role is controversial because it appears to be beneficial under some conditions and harmful in others. Now, Liu and colleagues have tried to address this question by examining the role of autophagy in melanoma.

The authors specifically focused on one regulator of autophagy, called autophagy-related protein 5 (ATG5). In a group of almost 200 patients with melanoma and 150 with benign melanocytic nevi, the authors saw decreased expression and increased methylation of ATG5 in the tumors compared to benign nevi and normal skin cells. Moreover, the extent of ATG5 expression in patients’ melanoma samples correlated with progression-free survival, such that patients with more ATG5 in their tumors had a better prognosis. Similarly, up-regulating ATG5 in cultured tumor cells inhibited their proliferation and caused them to undergo senescence.

The role of ATG5 in melanoma patients’ survival needs to be validated in additional human studies, and similar research should be performed for other types of cancer. Thus far, it can only serve as a prognostic marker, but future research may uncover ways to treat melanoma and other cancers by forcing the tumors to produce more ATG5 and literally eat themselves.