Downregulation of thrombomodulin, a novel target of snail, induces tumorigenesis through epithelial-mesenchymal transition

Yuan Chung Kao, Li Wha Wu, Chung Sheng Shi, Che Hsien Chu, Chia Wei Huang, Chou Pin Kuo, Hamm Ming Sheu, Guey Yueh Shi, Hua Lin Wu

研究成果: Article同行評審

35 引文 斯高帕斯(Scopus)

摘要

The expression of thrombomodulin (TM), a calcium-dependent adhesion molecule, is frequently downregulated in various cancer types. However, the mechanism responsible for the low expression level of TM in tumorigenesis is unknown. Here, an inverse expression of TM and Snail was detected in different cancer cell lines. We further confirmed this inverse relation using the epithelial-mesenchymal transition cell model in HaCaT and A431 cells. We demonstrated that Snail suppressed TM expression by binding to E-box (CACCTG) in TM promoter. Moreover, TM knockdown by short hairpin RNA disrupted E-cadherin-mediated cell junctions and contributed to tumorigenesis. In the calcium switch assay, E-cadherin lost the ability to associate withβ-catenin and accumulated in cytoplasm in TM knockdown cells. Meanwhile, wound healing and invasive assays showed that TM knockdown promoted cell motility. A subcutaneous injection of TM knockdown transfectants into immunocompromised mice induced squamous cell carcinoma-like tumors. Besides, forced expression of murine TM in TM knockdown cells made the cells reassume epithelium-like morphology and increased calcium-dependent association of E-cadherinand β-catenin. In conclusion, TM, a novel downstream target of Snail in epithelial-mesenchymal transition, is required for maintaining epithelial morphology and functions as a tumor suppressor.

原文English
頁(從 - 到)4767-4785
頁數19
期刊Molecular and Cellular Biology
30
發行號20
DOIs
出版狀態Published - 2010 十月

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

指紋 深入研究「Downregulation of thrombomodulin, a novel target of snail, induces tumorigenesis through epithelial-mesenchymal transition」主題。共同形成了獨特的指紋。

引用此