Role of transforming growth factor-beta signaling in cancer.

de Caestecker MP, Piek E, Roberts AB
J Natl Cancer Inst. 2000 92 (17): 1388-402

PMID: 10974075 · DOI:10.1093/jnci/92.17.1388

Signaling from transforming growth factor-beta (TGF-beta) through its unique transmembrane receptor serine-threonine kinases plays a complex role in carcinogenesis, having both tumor suppressor and oncogenic activities. Tumor cells often escape from the antiproliferative effects of TGF-beta by mutational inactivation or dysregulated expression of components in its signaling pathway. Decreased receptor function and altered ratios of the TGF-beta type I and type II receptors found in many tumor cells compromise the tumor suppressor activities of TGF-beta and enable its oncogenic functions. Recent identification of a family of intracellular mediators, the Smads, has provided new paradigms for understanding mechanisms of subversion of TGF-beta signaling by tumor cells. In addition, several proteins recently have been identified that can modulate the Smad-signaling pathway and may also be targets for mutation in cancer. Other pathways such as various mitogen-activated protein kinase cascades also contribute substantially to TGF-beta signaling. Understanding the interplay between these signaling cascades as well as the complex patterns of cross-talk with other signaling pathways is an important area of investigation that will ultimately contribute to understanding of the bifunctional tumor suppressor/oncogene role of TGF-beta in carcinogenesis.

MeSH Terms (14)

Animals DNA-Binding Proteins Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Humans Mutation Neoplasms Receptors, Transforming Growth Factor beta Signal Transduction Smad2 Protein Smad3 Protein Smad4 Protein Trans-Activators Transforming Growth Factor beta

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