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Review
. 2003 Mar;94(3):230-4.
doi: 10.1111/j.1349-7006.2003.tb01425.x.

Regulation of TGF-beta signaling and its roles in progression of tumors

Kohei Miyazono  1 , Hiroyuki Suzuki, Takeshi Imamura
Affiliations
Review

Regulation of TGF-beta signaling and its roles in progression of tumors

Kohei Miyazono et al. Cancer Sci. 2003 Mar.

Abstract

Transforming growth factor-beta (TGF-beta) is a potent growth inhibitor of most types of cells; therefore, perturbations of TGF-beta signaling are believed to result in progression of various tumors. On the other hand, TGF-beta has been shown to act as an oncogenic cytokine through induction of extracellular matrices, angiogenesis, and immune suppression. A wide variety of effects of TGF-beta 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-beta signaling is regulated by various mechanisms in the cytoplasm and nucleus. Inhibitory Smads (I-Smads) repress TGF-beta signaling mainly by interacting with activated TGF-beta receptors. Smad ubiquitin regulatory factors (Smurfs) play important roles in facilitating the inhibitory signals induced by I-Smads. In addition, the transcriptional co-repressors c-Ski and SnoN interact with Smads, and repress transcription induced by TGF-beta. Abnormalities of these regulators of TGF-beta signaling may thus participate in the progression of various tumors.

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