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Biol Pharm Bull. 2000 Oct;23(10):1125-30.

TGF-beta/SMAD signaling and its involvement in tumor progression.

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Department of Biochemistry, The Center Institute of the Japanese Foundation for Cancer Research, Tokyo, Japan.


Cytokines of the transforming growth factor-beta (TGF-beta) superfamily are multifunctional peptides that regulate growth and differentiation of various types of cells. Members of the TGF-beta superfamily bind to type 11 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-beta 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-beta/SMAD signaling. Perturbation of the TGF-beta/SMAD signaling pathway may result in progression of tumors through resistance of the cells to the growth inhibition induced by TGF-beta.

[Indexed for MEDLINE]

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