Regulation of TGF-beta signaling and its roles in progression of tumors.
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.
Miyazono
Kohei
K
Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Japan. miyazono-ind@umin.ac.jp
Suzuki
Hiroyuki
H
Imamura
Takeshi
T
D000818:Animals; D018450:Disease Progression; D005753:Gastric Mucosa / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta