Growth Factor Signaling Pathways as Targets for Prevention of Epithelial Carcinogenesis

Mol Carcinog. 2011 Apr;50(4):264-79. doi: 10.1002/mc.20665. Epub 2010 Jul 20.

Abstract

Growth factor receptor (GFR) signaling controls epithelial cell growth by responding to various endogenous or exogenous stimuli and subsequently activating downstream signaling pathways including Stat3, PI3K/Akt/mTOR, MAPK, and c-Src. Environmental chemical toxicants and UVB irradiation cause enhanced and prolonged activation of GFR signaling and downstream pathways that contributes to epithelial cancer development including skin cancer. Recent studies, especially those with tissue-specific transgenic mouse models, have demonstrated that GFRs and their downstream signaling pathways contribute to all three stages of epithelial carcinogenesis by regulating a wide variety of biological functions including proliferation, apoptosis, angiogenesis, cell adhesion, and migration. Inhibiting these signaling pathways early in the carcinogenic process results in reduced cell proliferation and survival, leading to decreased tumor formation. Collectively, these studies suggest that GFR signaling and subsequent downstream signaling pathways are potential targets for the prevention of epithelial cancers including skin cancer.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Humans
  • Models, Biological
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Growth Factor / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Antineoplastic Agents
  • Receptors, Growth Factor
  • Receptor, IGF Type 1