Actions of TGF-beta as tumor suppressor and pro-metastatic factor in human cancer

Biochim Biophys Acta. 2007 Jan;1775(1):21-62. doi: 10.1016/j.bbcan.2006.06.004. Epub 2006 Jul 8.


Transforming growth factor-beta (TGF-beta) is a secreted polypeptide that signals via receptor serine/threonine kinases and intracellular Smad effectors. TGF-beta inhibits proliferation and induces apoptosis in various cell types, and accumulation of loss-of-function mutations in the TGF-beta receptor or Smad genes classify the pathway as a tumor suppressor in humans. In addition, various oncogenic pathways directly inactivate the TGF-beta receptor-Smad pathway, thus favoring tumor growth. On the other hand, all human tumors overproduce TGF-beta whose autocrine and paracrine actions promote tumor cell invasiveness and metastasis. Accordingly, TGF-beta induces epithelial-mesenchymal transition, a differentiation switch that is required for transitory invasiveness of carcinoma cells. Tumor-derived TGF-beta acting on stromal fibroblasts remodels the tumor matrix and induces expression of mitogenic signals towards the carcinoma cells, and upon acting on endothelial cells and pericytes, TGF-beta regulates angiogenesis. Finally, TGF-beta suppresses proliferation and differentiation of lymphocytes including cytolytic T cells, natural killer cells and macrophages, thus preventing immune surveillance of the developing tumor. Current clinical approaches aim at establishing novel cancer drugs whose mechanisms target the TGF-beta pathway. In conclusion, TGF-beta signaling is intimately implicated in tumor development and contributes to all cardinal features of tumor cell biology.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neoplasm / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Carcinogens*
  • Cell Cycle / drug effects
  • Cell Transformation, Neoplastic / pathology
  • Disease Models, Animal
  • Epigenesis, Genetic
  • Epithelial Cells / pathology
  • Humans
  • Mesoderm / pathology
  • Mice
  • Mutation
  • Neoplasm Invasiveness / physiopathology
  • Neoplasm Metastasis / physiopathology
  • Neoplasms / blood supply
  • Neovascularization, Pathologic
  • Oncogenes / physiology
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Smad Proteins / genetics
  • Smad Proteins / physiology
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / physiology*
  • Tumor Suppressor Proteins / physiology*


  • Antibodies, Neoplasm
  • Carcinogens
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins