Duel nature of TGF-β signaling:: tumor suppressor vs. tumor promoter

被引:159
作者
Bachman, KE
Park, BH
机构
[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA
[2] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA
关键词
TGF-beta; cancer; p21; Smad;
D O I
10.1097/01.cco.0000143682.45316.ae
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of review Transforming growth factor beta type I (TGF-beta) is a ubiquitous cytokine that is well known for its ability to inhibit epithelial cell proliferation. Somatic mutations abrogating the TGF-beta signal transduction pathway are found in many gastrointestinal cancers, confirming its importance as a tumor suppressor. In contrast, many non gastrointestinal epithelial malignancies lack these somatic alterations, yet these cancers still acquire resistance to the growth-inhibitory effects of TGF-beta. In many instances, this resistance is part of a signaling switch whereby TGF-beta loses its growth inhibitory effects and is then used by the epithelial cell in a growth-promoting fashion. The mechanisms that underlie this change in the phenotypic growth response to TGF-beta are now being elucidated. This review focuses on recent advances in understanding the dual nature of the TGF-beta pathway as it relates to human carcinogenesis. Recent findings Elucidating the molecular basis that enables epithelial to change from a growth-suppressive to gowth-stimulatory phenotype on TGF-beta exposure is an area of active research. Besides enhancing cancer cell growth, TGF-beta is also thought to promote a malignant cell's ability to metastasize by mediating changes in the cytoskeletal architecture, known as an epithelial-to-mesenchymal transition. This process a cancer cell to invade and spread to distal sites. Strong evidence has now emerged cell to use TGF-beta as a grow is a result of a number of different factors, including the abser ty of cycle regulators may be the key element that dictates a cell's response to TGF-beta as growth-inhibitory versus growth-stimulatory, thus explaining the dual nature of TGF-beta signaling. Summary Current studies are beginning to shed light on the mechanisms that allow some nongastrointestinal epithelial cancers to evade the growth inhibitory effects of TGF-beta while simultaneously using this cytokine for growth advantage. By dissecting this phenotypic switch during tumor development, important genes, proteins, and pathways that are involved with TGF-beta signaling continue to be discovered. Knowledge of how premalignant cells
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页码:49 / 54
页数:6
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