Apoptosis and autophagy: Targeting autophagy signalling in cancer cells -'trick or treats'?

FEBS J. 2009 Nov;276(21):6084-96. doi: 10.1111/j.1742-4658.2009.07332.x. Epub 2009 Sep 29.

Abstract

Macroautophagy (hereafter referred to as autophagy) is a tightly regulated lysosome-dependent catabolic pathway. During this process, cytosolic constituents are sequestered into autophagosomes, which subsequently fuse with lysosomes to become autolysosomes, where their contents are degraded. Autophagy contributes to the maintenance of the cellular energy homeostasis, to the clearance of damaged organelles and to adaptation to environmental stresses. Accordingly, autophagy defects have been linked to a wide range of human pathologies, including cancer. The recent discovery of several evolutionarily conserved genes involved in autophagosome formation has greatly stimulated the autophagy research, and the complex signalling networks regulating mammalian autophagy have begun to emerge. Here, we draw the current picture of signalling pathways connecting mitogenic and stress-induced signals to the initiation and maturation of autophagosomes and discuss the possibilities of their targeting as therapeutic adjuvants in anticancer therapy.

Publication types

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

MeSH terms

  • AMP-Activated Protein Kinases / physiology
  • Animals
  • Apoptosis*
  • Autophagy* / drug effects
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes
  • Neoplasms / drug therapy
  • Neoplasms / etiology
  • Neoplasms / pathology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Protein Phosphatase 2 / physiology
  • Proteins
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases
  • Transcription Factors / physiology

Substances

  • Multiprotein Complexes
  • Proteins
  • Transcription Factors
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • AMP-Activated Protein Kinases
  • Protein Phosphatase 2