Regulation of TGF‐β signaling and its roles in progression of tumors

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Abstract
Transforming growth factor‐β (TGF‐β) is a potent growth inhibitor of most types of cells; therefore, perturbations of TGF‐β signaling are believed to result in progression of various tumors. On the other hand, TGF‐β has been shown to act as an oncogenic cyto‐kine through induction of extracellular matrices, angiogenesis, and immune suppression. A wide variety of effects of TGF‐p are mediated by physical interaction of signal transducer Smad proteins with various transcription factors. Among these, Runx3 plays a pivotal role in prevention of gastric cancer. TGF‐β signaling is regulated by various mechanisms in the cytoplasm and nucleus. Inhibitory Smads (l‐Smads) repress TGF‐β signaling mainly by interacting with activated TGF‐β receptors. Smad ubiquitin regulatory factors (Smurfs) play important roles in facilitating the inhibitory signals induced by l‐Smads. In addition, the transcrip‐tional co‐repressors c‐Ski and SnoN interact with Smads, and repress transcription induced by TGF‐β. Abnormalities of these regulators of TGF‐β signaling may thus participate in the progression of various tumors. (Cancer Sci 2003; 94: 230–234)