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

Cancer Cell
Authors
Keywords
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.

Year of Publication
2013
Journal
Cancer Cell
Volume
23
Issue
3
Pages
287-301
Date Published
2013 Mar 18
ISSN
1878-3686
DOI
10.1016/j.ccr.2012.11.020
PubMed ID
23416000
PubMed Central ID
PMC3708305
Links
Grant list
P50 CA093683 / CA / NCI NIH HHS / United States
R01 CA169919 / CA / NCI NIH HHS / United States
P50CA093683 / CA / NCI NIH HHS / United States