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

Détails

ID Serval
serval:BIB_8DF43A4C635E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
AMPK promotes survival of c-Myc-positive melanoma cells by suppressing oxidative stress.
Périodique
The EMBO journal
Auteur(s)
Kfoury A., Armaro M., Collodet C., Sordet-Dessimoz J., Giner M.P., Christen S., Moco S., Leleu M., de Leval L., Koch U., Trumpp A., Sakamoto K., Beermann F., Radtke F.
ISSN
1460-2075 (Electronic)
ISSN-L
0261-4189
Statut éditorial
Publié
Date de publication
01/03/2018
Peer-reviewed
Oui
Volume
37
Numéro
5
Pages
e97673
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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 <i>Nras</i> <sup>
<i>Q61K</i>
</sup> <i>INK4a</i> <sup>-/-</sup> 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.
Mots-clé
AMP-Activated Protein Kinases/genetics, AMP-Activated Protein Kinases/metabolism, Animals, Apoptosis/genetics, Cell Line, Tumor, Cell Survival, Cell Transformation, Neoplastic/genetics, Cyclin-Dependent Kinase Inhibitor p16/genetics, GTP Phosphohydrolases/metabolism, Gene Expression Regulation, Neoplastic/genetics, Humans, Melanocytes/pathology, Melanoma/pathology, Membrane Proteins/metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Oxidative Stress/physiology, Prognosis, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/metabolism, RNA Interference, RNA, Small Interfering/genetics, Signal Transduction, AMPK, c‐Myc, gene targeting, melanoma, oxidative stress
Pubmed
Web of science
Création de la notice
15/02/2018 18:48
Dernière modification de la notice
19/12/2018 7:26
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