Role of transforming growth factor Beta in human cancer

J Clin Oncol. 2005 Mar 20;23(9):2078-93. doi: 10.1200/JCO.2005.02.047.


Transforming growth factor beta (TGF-beta) is a ubiquitous and essential regulator of cellular and physiologic processes including proliferation, differentiation, migration, cell survival, angiogenesis, and immunosurveillance. Alterations in the TGF-beta signaling pathway, including mutation or deletion of members of the signaling pathway and resistance to TGF-beta-mediated inhibition of proliferation are frequently observed in human cancers. Although these alterations define a tumor suppressor role for the TGF-beta pathway in human cancer, TGF-beta also mediates tumor-promoting effects, either through differential effects on tumor and stromal cells or through a fundamental alteration in the TGF-beta responsiveness of the tumor cells themselves. TGF-beta and members of the TGF-beta signaling pathway are being evaluated as prognostic or predictive markers for cancer patients. Ongoing advances in understanding the TGF-beta signaling pathway will enable targeting of this pathway for the chemoprevention and treatment of human cancers.

Publication types

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

MeSH terms

  • Apoptosis / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Humans
  • Neoplasm Metastasis
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Smad4 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transforming Growth Factor beta / biosynthesis
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / physiology*


  • DNA-Binding Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Trans-Activators
  • Transforming Growth Factor beta