Feb 15, 2018

AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress

The EMBO Journal
Alain KfouryFreddy Radtke

Abstract

Although c-Myc is essential for melanocyte development, its role in cutaneous melanoma, the most aggressive skin cancer, is only partly understood. Here we used the Nras Q61K INK4a-/- mouse melanoma model to show that c-Myc is essential for tumor initiation, maintenance, and metastasis. c-Myc-expressing melanoma cells were preferentially found at metastatic sites, correlated with increased tumor aggressiveness and high tumor initiation potential. Abrogation of c-Myc caused apoptosis in primary murine and human melanoma cells. Mechanistically, c-Myc-positive melanoma cells activated and became dependent on the metabolic energy sensor AMP-activated protein kinase (AMPK), a metabolic checkpoint kinase that plays an important role in energy and redox homeostasis under stress conditions. AMPK pathway inhibition caused apoptosis of c-Myc-expressing melanoma cells, while AMPK activation protected against cell death of c-Myc-depleted melanoma cells through suppression of oxidative stress. Furthermore, TCGA database analysis of early-stage human melanoma samples revealed an inverse correlation between C-MYC and patient survival, suggesting that C-MYC expression levels could serve as a prognostic marker for early-stage disease.

  • References57
  • Citations7

Mentioned in this Paper

Malignant Neoplasm of Skin
Biological Markers
Metabolic Process, Cellular
HRAS
Biochemical Pathway
Melanocyte
Gene Expression Regulation, Neoplastic
MYC protein, human
NRAS gene
N-ras Genes

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