Four-and-a-half LIM protein 2 promotes invasive potential and epithelial-mesenchymal transition in colon cancer
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摘要Background and Aims: Cancer invasion and metastasis may associate with the phenotype transition called epithelial-mesenchymal transition (EMT). We aim to evaluate the impact of four-and-a-half LIM protein 2 (FHL2) on EMT and invasion of colon cancer. Methods: The functional role of FHL2 in EMT was determined by overexpression or small interfering RNA-mediated depletion of FHL2. Mechanisms of FHL2 on expression or activity of E-cadherin and beta-catenin were assessed. Results: FHL2 was highly expressed in primary and metastatic colon cancer but not in normal tissues. FHL2 was critical for cancer cell adhesion to extracellular matrix, migration and invasion. FHL2 expression was stimulated by transforming growth factor (TGF)-beta 1. Moreover, FHL2 acted as a potent EMT inducer by stimulating vimentin and matrix metalloproteinase-9 expressions and causing a loss of E-cadherin, whereas those alterations of EMT markers were not affected by silencing of Smad molecules (typical TGF-beta signal mediators) in FHL2 stable transfectant cells. Therefore, FHL2 induced EMT in a TGF-beta-dependent and Smad-independent manner. FHL2 downregulated E-cadherin expression and inhibited the formation of membrane-associated E-cadherin-beta-catenin complex. FHL2 also stabilized nuclear beta-catenin, resulting in enforcement of beta-catenin transactivation activity. Conclusion: FHL2 is a potent EMT inducer and might be an important mediator for invasion and/or metastasis of colon cancer.
著者Zhang WJ, Jiang B, Guo Z, Sardet C, Zou B, Lam CS, Li JM, He ML, Lan HY, Pang R, Hung IFN, Tan VPY, Wang JD, Wong BCY
期刊名稱Carcinogenesis
出版年份2010
月份7
日期1
卷號31
期次7
出版社Oxford University Press (OUP): Policy B - Oxford Open Option B
頁次1220 - 1229
國際標準期刊號0143-3334
電子國際標準期刊號1460-2180
語言英式英語
Web of Science 學科類別Oncology; ONCOLOGY

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