| First Author | Kfoury A | Year | 2018 |
| Journal | EMBO J | Volume | 37 |
| Issue | 5 | PubMed ID | 29440228 |
| Mgi Jnum | J:317537 | Mgi Id | MGI:6856268 |
| Doi | 10.15252/embj.201797673 | Citation | Kfoury A, et al. (2018) AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress. EMBO J 37(5) |
| abstractText | 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. |
