TGF-beta and colorectal carcinogenesis

There is substantial evidence to support the contention that the Smad porti on of the TGF-beta signal transduction pathway provides an important tumor- suppressor function. Mutational loss of function of Smad pathway members ha ve been associated with the development of human cancers and appear to be c ausative in selected rodent carcinogenesis models. TGF-beta also has multip le other actions that appear to be independent of the growth-inhibitory/tum or suppressor effects. The predominant effect of TGF-beta appears to be dep endent on the context of the responding cell. Once transformation has occur red, TGF-beta effects may be detrimental and may actually promote tumor cel l survival, invasion, and metastasis. Recent work suggests that these effec ts may involve TGF-beta regulation of COX-2 and other pathways that may con tribute to tumor cell aggressiveness. In gaining a better understanding of the mechanisms by which TGF-beta may promote tumor progression, it is likel y that new therapeutic strategies may be developed that preserve tumor-supp ressor function of TGF-beta while inhibiting the tumor-promoting effects. M icrosc. Res. Tech. 52: 450-457, 2001. (C) 2001 Wiley-Liss, Inc.