PGC1α Expression Defines a Subset of Human Melanoma Tumors With Increased Mitochondrial Capacity and Resistance to Oxidative Stress

Cancer Cell. 2013 Mar 18;23(3):287-301. doi: 10.1016/j.ccr.2012.11.020. Epub 2013 Feb 14.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Energy Metabolism
  • HEK293 Cells
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism*
  • Humans
  • Melanocytes / metabolism*
  • Melanoma / metabolism*
  • Mice
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Mitochondria / metabolism*
  • Oxidative Stress*
  • Oxygen Consumption
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA Interference
  • RNA, Small Interfering
  • Reactive Oxygen Species / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Heat-Shock Proteins
  • MITF protein, human
  • Microphthalmia-Associated Transcription Factor
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Transcription Factors

Associated data

  • GEO/GSE36879