REVIEW Escaping from the TGFb anti-proliferative control

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