AMPK, the metabolic syndrome and cancer

Trends Pharmacol Sci. 2005 Feb;26(2):69-76. doi: 10.1016/j.tips.2004.12.011.

Abstract

The fuel-sensing enzyme 5'-AMP-activated protein kinase (AMPK) has a major role in the regulation of cellular lipid and protein metabolism in response to stimuli such as exercise, changes in fuel availability and the adipocyte-derived hormones leptin and adiponectin. Recent studies indicate that abnormalities in cellular lipid metabolism are involved in the pathogenesis of the metabolic syndrome, possibly because of dysregulation of AMPK and malonyl-CoA, a closely related molecule. As we discuss in this article, several findings also point to a link between AMPK and the growth and/or survival of some cancer cells. Thus, it has been demonstrated recently that the tumor suppressor LKB1 is a kinase that has a major role in phosphorylating and activating AMPK, and that another tumor suppressor, tuberous sclerosis complex 2, is phosphorylated and activated by AMPK. In addition, other studies indicate that mammalian homolog of target of rapamycin (mTOR), which has been implicated in the pathogenesis of insulin resistance and many types of cancer, is inhibited by AMPK.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Expert Testimony / trends
  • Genetic Predisposition to Disease
  • Humans
  • Metabolic Syndrome / etiology*
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism
  • Multienzyme Complexes / drug effects
  • Multienzyme Complexes / physiology*
  • Multienzyme Complexes / therapeutic use
  • Neoplasms / etiology*
  • Neoplasms / physiopathology
  • Protein-Serine-Threonine Kinases / drug effects
  • Protein-Serine-Threonine Kinases / physiology*
  • Protein-Serine-Threonine Kinases / therapeutic use

Substances

  • Multienzyme Complexes
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases