TGF-β: duality of function between tumor prevention and carcinogenesis

J Natl Cancer Inst. 2014 Feb;106(2):djt369. doi: 10.1093/jnci/djt369.

Abstract

Several mechanisms underlying tumor progression have remained elusive, particularly in relation to transforming growth factor beta (TGF-β). Although TGF-β initially inhibits epithelial growth, it appears to promote the progression of advanced tumors. Defects in normal TGF-β pathways partially explain this paradox, which can lead to a cascade of downstream events that drive multiple oncogenic pathways, manifesting as several key features of tumorigenesis (uncontrolled proliferation, loss of apoptosis, epithelial-to-mesenchymal transition, sustained angiogenesis, evasion of immune surveillance, and metastasis). Understanding the mechanisms of TGF-β dysregulation will likely reveal novel points of convergence between TGF-β and other pathways that can be specifically targeted for therapy.

Publication types

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

MeSH terms

  • Animals
  • Anticarcinogenic Agents* / metabolism
  • Anticarcinogenic Agents* / pharmacology
  • Apoptosis*
  • Cadherins / metabolism
  • Carcinogenesis / metabolism
  • Carcinogens* / metabolism
  • Carcinogens* / pharmacology
  • Cell Proliferation*
  • Cell Transformation, Neoplastic* / chemically induced
  • Cell Transformation, Neoplastic* / metabolism
  • Disease Progression
  • Humans
  • Neoplasms / chemically induced
  • Neoplasms / metabolism*
  • Neoplasms / prevention & control
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / prevention & control
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation

Substances

  • Anticarcinogenic Agents
  • Cadherins
  • Carcinogens
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein-Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I