Regulation of TGF-beta signaling and its roles in progression of tumors

Cancer Sci. 2003 Mar;94(3):230-4. doi: 10.1111/j.1349-7006.2003.tb01425.x.


Transforming growth factor-beta (TGF-beta) is a potent growth inhibitor of most types of cells; therefore, perturbations of TGF-beta signaling are believed to result in progression of various tumors. On the other hand, TGF-beta has been shown to act as an oncogenic cytokine through induction of extracellular matrices, angiogenesis, and immune suppression. A wide variety of effects of TGF-beta are mediated by physical interaction of signal transducer Smad proteins with various transcription factors. Among these, Runx3 plays a pivotal role in prevention of gastric cancer. TGF-beta signaling is regulated by various mechanisms in the cytoplasm and nucleus. Inhibitory Smads (I-Smads) repress TGF-beta signaling mainly by interacting with activated TGF-beta receptors. Smad ubiquitin regulatory factors (Smurfs) play important roles in facilitating the inhibitory signals induced by I-Smads. In addition, the transcriptional co-repressors c-Ski and SnoN interact with Smads, and repress transcription induced by TGF-beta. Abnormalities of these regulators of TGF-beta signaling may thus participate in the progression of various tumors.

Publication types

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

MeSH terms

  • Animals
  • Disease Progression
  • Gastric Mucosa / pathology
  • Humans
  • Models, Biological
  • Neoplasms / pathology*
  • Neoplasms / physiopathology*
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / physiology*


  • Transforming Growth Factor beta