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

• Published in: Carcinogenesis (New York) Vol. 31; no. 7; pp. 1220 - 1229
• Main Authors: Zhang, Wenjing, Jiang, Bo, Guo, Zheng, Sardet, Claude, Zou, Bing, Lam, Colin S.C., Li, Jianming, He, Mingliang, Lan, Hui-Yao, Pang, Roberta, Hung, I.F.N., Tan, V.P.Y., Wang, Jide, Wong, Benjamin C.Y.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-07-2010
• Subjects: Animals; beta Catenin - metabolism; Biochemistry, Molecular Biology; Biological and medical sciences; Cadherins - analysis; Carcinogenesis, carcinogens and anticarcinogens; Cell Adhesion; Cell Movement; Colonic Neoplasms - pathology; Epithelial Cells - pathology; Gastroenterology. Liver. Pancreas. Abdomen; HCT116 Cells; Homeodomain Proteins - analysis; Homeodomain Proteins - physiology; Humans; Life Sciences; LIM-Homeodomain Proteins; Medical sciences; Mesoderm - pathology; Mice; Muscle Proteins - analysis; Muscle Proteins - physiology; Neoplasm Invasiveness; Neoplasm Metastasis; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transcription Factors - analysis; Transcription Factors - physiology; Tumors; Colonic disease; Colon cancer; Digestive diseases; Intestinal disease; Malignant tumor; Mesenchymal cell; Protein; Cancer; Animals Cadherins/analysis Cell Adhesion Cell Movement Colonic Neoplasms/pathology Epithelial Cells/pathology HCT116 Cells Homeodomain Proteins/analysis/physiology Humans Mesoderm/pathology Mice Muscle Proteins/analysis/physiology Neoplasm Invasiveness Neoplasm Metastasis Transcription Factors/analysis/physiology beta Catenin/metabolism
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgq094

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.