TGF-beta and colorectal carcinogenesis.
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.
Roman
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Department of Surgery, Vanderbilt University Medical Center and the Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA.
Saha
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Beauchamp
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D000236:Adenoma / Q000276:immunology / Q000503:physiopathology*; D000818:Animals; D015179:Colorectal Neoplasms / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta