TGF-beta/SMAD signaling and its involvement in tumor progression

Biol Pharm Bull. 2000 Oct;23(10):1125-30. doi: 10.1248/bpb.23.1125.


Cytokines of the transforming growth factor-beta (TGF-beta) superfamily are multifunctional peptides that regulate growth and differentiation of various types of cells. Members of the TGF-beta superfamily bind to type 11 and type I serine/threonine kinase receptors, which mediate intracellular signals through SMAD proteins. Of 3 subtypes of SMADs, receptor-regulated SMADs are phosphorylated by the serine/threonine kinase receptors, form complexes with common-mediator SMAD, and move into the nucleus, where they act as components of transcription factor complexes. Abnormalities of the TGF-beta receptors and SMADs have been detected in various tumors, including colorectal cancers and pancreatic cancers. Inhibitory SMADs and transcriptional co-repressors, including c-Ski and SnoN, repress the TGF-beta/SMAD signaling. Perturbation of the TGF-beta/SMAD signaling pathway may result in progression of tumors through resistance of the cells to the growth inhibition induced by TGF-beta.

Publication types

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

MeSH terms

  • Animals
  • Disease Progression
  • Humans
  • Neoplasms / pathology*
  • Signal Transduction / physiology*
  • Transcription Factors / physiology*
  • Transforming Growth Factor beta / physiology*


  • Transcription Factors
  • Transforming Growth Factor beta