Past, present, and emerging roles of mitochondrial heat shock protein TRAP1 in the metabolism and regulation of cancer stem cells

Cell Stress Chaperones. 2016 Jul;21(4):553-62. doi: 10.1007/s12192-016-0687-3. Epub 2016 Apr 12.

Abstract

Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the HSP90 family, controls a variety of physiological functions, including cell proliferation, differentiation, and survival. Most studies have been devoted to understanding the anti-apoptotic roles of TRAP1 in cancer and targeting it for tumor control in clinical settings. Additionally, we have identified a new role for TRAP1 in regulation of liver regeneration after partial hepatectomy in TRAP1 transgenic mice and cellular proliferation in TRAP1-overexpressing cells, via mitochondrial alterations. Moreover, recent works have indicated a role for TRAP1 in the regulation of cancer stem cells (CSCs) as well as a metabolic switch between mitochondrial respiration and aerobic glycolysis called as "Warburg effect." This review discusses the implications of TRAP1 action for both metabolism and the regulation of CSCs.

Keywords: Apoptosis; Cancer stem cells; Fatty liver; TRAP1; Warburg effect.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Proliferation
  • Cellular Senescence / physiology
  • Glycolysis / physiology
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • Liver Regeneration / physiology
  • Mice
  • Mitochondria / metabolism*
  • Neoplastic Stem Cells / metabolism*

Substances

  • HSP90 Heat-Shock Proteins
  • TRAP1 protein, human