Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

Aging (Albany NY). 2011 Mar;3(3):192-222. doi: 10.18632/aging.100296.

Abstract

Dysregulated signaling through the Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is often the result of genetic alterations in critical components in these pathways or upstream activators. Unrestricted cellular proliferation and decreased sensitivity to apoptotic-inducing agents are typically associated with activation of these pro-survival pathways. This review discusses the functions these pathways have in normal and neoplastic tissue growth and how they contribute to resistance to apoptotic stimuli. Crosstalk and commonly identified mutations that occur within these pathways that contribute to abnormal activation and cancer growth will also be addressed. Finally the recently described roles of these pathways in cancer stem cells, cellular senescence and aging will be evaluated. Controlling the expression of these pathways could ameliorate human health.

Publication types

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

MeSH terms

  • Aging / drug effects
  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Apoptosis
  • Cell Proliferation
  • Cellular Senescence
  • Female
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Models, Biological
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / therapy
  • PTEN Phosphohydrolase
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / metabolism
  • raf Kinases / metabolism

Substances

  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • raf Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human