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KMID : 1140120090140040283
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Cancer Prevention Research
2009 Volume.14 No. 4 p.283 ~ p.291
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Cancer Prevention through Regulation of TGF-? Signaling-related Inflammatory Processes
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Kim Yoon-Jae
Hong Sun-Taek
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Abstract
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Transforming growth factor-? (TGF-?) has a dual role in tumorigenesis as a tumor suppressor or a tumor promoter. In normal cells, TGF-? suppresses the initiation of cell transformation by inhibiting cell growth and inducing cell apoptosis. However, TGF-? also modulates processes such as motility, invasion, immune surveillance and angiogenesis of tumorigenic cells in their late stage or metastatic stage. These paradoxical characteristics may depend on contextual, developmental and tissue-specific conditions. Cross-talk between tumor cells and their surrounding microenvironment is crucial during tumorigenesis. In particular, inflammatory microenvironment can induce cells to undergo transformations by supplying inflammatory cytokines and inhibiting immune system. Because TGF-?has been known to suppress immune system, it is important to understand the regulation of inflammatory signaling by TGF-? during tumorigenesis. Our group has published that TGF-? signaling mediators such as Smad6 and Smad7 inhibit inflammatory processes by blocking the recruitment of adaptors to cognate receptors and mediating the anti-inflammatory function of TGF-?. Based on the previous data, it will be useful to find new therapeutic reagents that can specifically induce Smad proteins or inhibit inflammatory signaling through high- throughput screening of natural products or chemical library.
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KEYWORD
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TGF-β, Inflammation, Tumorigenesis, Smad7
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