Escaping from the TGFbeta anti-proliferative control.

Transforming growth factor-beta (TGFbeta) has a crucial role in tissue homeostasis and disruption of the TGFbeta pathway has been implicated in many human diseases including cancer. As a potent inhibitor of epithelial cell proliferation, TGFbeta is a tumor suppressor. Tumor cells evade the antitumoral effect of TGFbeta, either by acquiring somatic mutations that blunt TGFbeta signaling or by selectively preventing the cytostatic responses to TGFbeta. During tumor progression, TGFbeta not only loses the anti-proliferative response but can also become an oncogenic factor. Recent work has provided insights into the specific molecular mechanisms involved in the loss of the TGFbeta anti-proliferative response. This review is an overview of the mechanisms that lead to the impairment of the tumor-suppressive function of TGFbeta in cancer. The understanding of how the TGFbeta signal is disrupted in cancer might facilitate the design and development of rational and successful therapeutic strategies.