Journal Article

Four-and-a-half LIM protein 2 promotes invasive potential and epithelial-mesenchymal transition in colon cancer

Wenjing Zhang, Bo Jiang, Zheng Guo, Claude Sardet, Bing Zou, Colin S.C. Lam, Jianming Li, Mingliang He, Hui-Yao Lan, Roberta Pang, I.F.N. Hung, V.P.Y. Tan, Jide Wang and Benjamin C.Y. Wong

in Carcinogenesis

Volume 31, issue 7, pages 1220-1229
Published in print July 2010 | ISSN: 0143-3334
Published online May 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq094
Four-and-a-half LIM protein 2 promotes invasive potential and epithelial-mesenchymal transition in colon cancer

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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 β-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)-β1. 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-β signal mediators) in FHL2 stable transfectant cells. Therefore, FHL2 induced EMT in a TGF-β-dependent and Smad-independent manner. FHL2 downregulated E-cadherin expression and inhibited the formation of membrane-associated E-cadherin–β-catenin complex. FHL2 also stabilized nuclear β-catenin, resulting in enforcement of β-catenin transactivation activity. Conclusion: FHL2 is a potent EMT inducer and might be an important mediator for invasion and/or metastasis of colon cancer.

Journal Article.  5351 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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