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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,
Benjamin C Y Wong
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ABSTRACT: 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.
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.
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)-beta1. 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.
FHL2 is a potent EMT inducer and might be an important mediator for invasion and/or metastasis of colon cancer.
Carcinogenesis 05/2010; 31(7):1220-9. · 5.70 Impact Factor
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ABSTRACT: Familial non-autoimmune hyperthyroidism is a rare autosomal dominant genetic disease resulting from activating mutations in the thyroid-stimulating hormone receptor (TSHR) gene. In this work a Chinese family with autosomal dominant non-autoimmune hyperthyroidism across four generations was collected. The strongest evidence for linkage in this study occurred on chromosome 14q24.2-31.3. By mutation scan of the TSHR gene located within the region of interest, a heterozygote substitution (A > T) at position 2071 of the TSHR was found, changing isoleucine 691 to phenylalanine. Our study identified the first germline mutation in the intracellular C-terminal domain of TSHR.
Journal of Human Genetics 01/2008; 53(5):475-8. · 2.57 Impact Factor
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Xiang-Ping Li,
Christine Y S Li,
Xiaohua Li,
Yanqing Ding,
Lally L Y Chan,
Pai-Hao Yang,
Gang Li,
Xiong Liu,
Jennifer S Lin,
Jide Wang, Mingliang He,
Hsiang-Fu Kung,
Marie C Lin,
Ying Peng
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ABSTRACT: Nasopharyngeal carcinoma (NPC) is a highly malignant and frequently metastasized tumor. Endostatin has been shown to inhibit NPC growth, but its efficacy against NPC metastasis has not been shown in vivo. Here, we established a NPC metastasis model in mice by transplanting EBV-positive NPC cells, C666-1, in the livers of nude mice and observed lung metastasis. Furthermore, we showed that tail vein injection of recombinant adeno-associated virus encoding human endostatin (rAAV-hEndo) significantly prolonged the median survival rate of NPC metastasis-bearing mice (from 22 to 37 days, P < 0.01). The rAAV-hEndo treatment resulted in a statistically significant reduction in tumor growth and microvessel formation. It also increased the apoptotic index in the primary liver tumor but not in the normal liver tissue. Importantly, no formation of liver or lung metastasis was detected. The potent inhibition of NPC metastasis suggests the feasibility of combining rAAV-hEndo gene therapy with other therapies for the prevention and treatment of NPC metastasis.
Molecular Cancer Therapeutics 05/2006; 5(5):1290-8. · 5.23 Impact Factor
