Role of Transforming Growth Factor-[beta] Signaling in Cancer.
de Caestecker, Mark P.; Piek, Ester; Roberts, Anita B.
[Review]
Journal of the National Cancer Institute.
92(17):1388-1402, September 6, 2000.
(Format: HTML, PDF)
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.
(C) Copyright Oxford University Press 2000.