Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
TGF-β/SMAD Signaling and Its Involvement in Tumor Progression
Kohei MIYAZONO
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2000 年 23 巻 10 号 p. 1125-1130

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Cytokines of the transforming growth factor-β(TGF-β) superfamily are multifunctional peptides that regulate growth and differentiation of various types of cells. Members of the TGF-β superfamily bind to type II and type I serine/threonine kinase receptors, which mediate intracellular signals through SMAD proteins. Of 3 subtypes of SMADs, receptor-regulated SMADs are phosphorylated by the serine/threonine kinase receptors, form complexes with common-mediator SMAD, and move into the nucleus, where they act as components of transcription factor complexes. Abnormalities of the TGF-β receptors and SMADs have been detected in various tumors, including colorectal cancers and pancreatic cancers. Inhibitory SMADs and transcriptional co-repressors, including c-Ski and SnoN, repress the TGF-β/SMAD signaling. Perturbation of the TGF-β/SMAD signaling pathway may result in progression of tumors through resistance of the cells to the growth inhibition induced by TGF-β.
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© The Pharmaceutical Society of Japan
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