TGF-beta and colorectal carcinogenesis

Microsc Res Tech. 2001 Feb 15;52(4):450-7. doi: 10.1002/1097-0029(20010215)52:4<450::AID-JEMT1030>3.0.CO;2-O.

Abstract

There is substantial evidence to support the contention that the Smad portion of the TGF-beta signal transduction pathway provides an important tumor-suppressor function. Mutational loss of function of Smad pathway members have been associated with the development of human cancers and appear to be causative in selected rodent carcinogenesis models. TGF-beta also has multiple other actions that appear to be independent of the growth-inhibitory/tumor suppressor effects. The predominant effect of TGF-beta appears to be dependent on the context of the responding cell. Once transformation has occurred, TGF-beta effects may be detrimental and may actually promote tumor cell survival, invasion, and metastasis. Recent work suggests that these effects may involve TGF-beta regulation of COX-2 and other pathways that may contribute to tumor cell aggressiveness. In gaining a better understanding of the mechanisms by which TGF-beta may promote tumor progression, it is likely that new therapeutic strategies may be developed that preserve tumor-suppressor function of TGF-beta while inhibiting the tumor-promoting effects.

Publication types

  • Review

MeSH terms

  • Adenoma / immunology
  • Adenoma / physiopathology*
  • Animals
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / physiopathology*
  • Humans
  • Mice
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / physiology
  • Signal Transduction
  • Transforming Growth Factor beta / physiology*

Substances

  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta