Vicious cycle of TGF-β signaling in tumor progression and metastasis.

TGF-β is an important biological mediator. It regulates a wide range of functions including embryonic development, wound healing, organ development, immuno-modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells, a phenomenon known as TGF-β paradox. TGF-β stimulation in cancer cells leads to a differential Erk activation, which srves as the basis of TGF-β paradox between benign and cancer cells. The critical events of TGF-β mediated Erk activation are suppressed TBRs and elevated TGF-β in tumor cells but not in benign cells. These events form the basis of the "vicious cycle of TGF-β signaling". The term "vicious cycle", implies that, with each advancing cycle of TGF-β signaling, the tumor will accumulate more TGF-β and will be more "aggressive" than that of the previous cycle. Understanding this vicious cycle of TGF-β signaling in tumor progression and metastasis will help us to predict indolent from aggressive cancers and will help us to develop novel anti-cancer strategies.