The PGC-1/ERR signaling axis in cancer

Oncogene. 2013 Jul 25;32(30):3483-90. doi: 10.1038/onc.2012.529. Epub 2012 Dec 3.

Abstract

Proliferating cells need to produce a large amount of energy and, at the same time, need to maintain a constant supply of biosynthetic precursors of macromolecules that are used as building blocks for generating new cells. Indeed, many cancer cells undergo a switch from mitochondrial to glycolytic metabolism and display a truncated tricarboxylic acid cycle to match these specific metabolic requirements of proliferation. Understanding the mechanisms by which cancer cells reprogram various metabolic pathways to satisfy their unique bioenergetic requirements has become an active field of research. Concomitantly, it has emerged that members of a family of orphan nuclear receptors known as the estrogen-related receptors (ERRs), working in concert with members of the PPARγ coactivator (PGC)-1 family, act as central transcriptional regulators of metabolic gene networks involved in maintaining energy homeostasis in normal cells. Recent studies have suggested that the PGC-1/ERR transcriptional axis is also important in the metabolic reprogramming of cancer cells. This review focuses on the functional integration of the PGC-1/ERR axis with known oncogenes and the observation that modulation of the activity of this axis can have both pro- and anti-proliferative properties.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • ERRalpha Estrogen-Related Receptor
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / physiology*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Receptors, Estrogen / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*

Substances

  • Heat-Shock Proteins
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Receptors, Estrogen
  • Transcription Factors