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Cancer Cell DOI:10.1016/j.ccr.2012.11.020

PGC1α expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress.

Publication TypeJournal Article
Year of Publication2013
AuthorsVazquez, F, Lim, J-H, Chim, H, Bhalla, K, Girnun, G, Pierce, K, Clish, CB, Granter, SR, Widlund, HR, Spiegelman, BM, Puigserver, P
JournalCancer Cell
Volume23
Issue3
Pages287-301
Date Published2013 Mar 18
ISSN1878-3686
KeywordsAnimals, Apoptosis, Cell Line, Tumor, Energy Metabolism, Heat-Shock Proteins, HEK293 Cells, Humans, Melanocytes, Melanoma, Mice, Microphthalmia-Associated Transcription Factor, Mitochondria, Oxidative Stress, Oxygen Consumption, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Reactive Oxygen Species, RNA Interference, RNA, Small Interfering, Transcription Factors
Abstract

Cancer cells reprogram their metabolism using different strategies to meet energy and anabolic demands to maintain growth and survival. Understanding the molecular and genetic determinants of these metabolic programs is critical to successfully exploit them for therapy. Here, we report that the oncogenic melanocyte lineage-specification transcription factor MITF drives PGC1α (PPARGC1A) overexpression in a subset of human melanomas and derived cell lines. Functionally, PGC1α positive melanoma cells exhibit increased mitochondrial energy metabolism and reactive oxygen species (ROS) detoxification capacities that enable survival under oxidative stress conditions. Conversely, PGC1α negative melanoma cells are more glycolytic and sensitive to ROS-inducing drugs. These results demonstrate that differences in PGC1α levels in melanoma tumors have a profound impact in their metabolism, biology, and drug sensitivity.

DOI10.1016/j.ccr.2012.11.020
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23416000?dopt=Abstract

Alternate JournalCancer Cell
PubMed ID23416000
PubMed Central IDPMC3708305
Grant ListP50 CA093683 / CA / NCI NIH HHS / United States
R01 CA169919 / CA / NCI NIH HHS / United States
P50CA093683 / CA / NCI NIH HHS / United States