Escaping from the TGFβ anti-proliferative control

Transforming growth factor-beta (TGF beta) has a crucial role in tissue homeostasis and disruption of the TGF beta pathway has been implicated in many human diseases including cancer. As a potent inhibitor of epithelial cell proliferation, TGF beta is a tumor suppressor. Tumor cells evade the antitumoral effect of TGF beta, either by acquiring somatic mutations that blunt TGF beta signaling or by selectively preventing the cytostatic responses to TGF beta. During tumor progression, TGF beta 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 TGF beta anti-proliferative response. This review is an overview of the mechanisms that lead to the impairment of the tumor-suppressive function of TGF beta in cancer. The understanding of how the TGF beta signal is disrupted in cancer might facilitate the design and development of rational and successful therapeutic strategies.