Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression

Annals of Surgical Oncology
Ming-Te HuangYu-Jia Chang

Abstract

Thrombomodulin (TM) is a key molecule mediating circulation homeostasis through its binding to thrombin. The TM-thrombin complex can activate protein C and thrombin-activatable fibrinolysis inhibitor to form a tight clot. In many cancer tissues, decrease of TM expression may correlate with cancer metastasis. However, the role of TM in hepatocellular carcinoma (HCC) progression is still unclear. We characterized TM expression in HCC cells (HepJ5 and skHep-1 cells) using real-time polymerase chain reaction (PCR) and Western blotting. We then manipulated TM expression using both TM-specific short hairpin RNA (shRNA) and overexpressing it in HCC cells. Transwell migration assay was performed to monitor the migratory ability of HCC cells under different levels of TM expression. We found that TM was ectopically highly expressed in skHep-1 at both transcriptional and translational levels. After silencing TM expression in skHep-1 cells, we found that metastatic capability was dramatically increased. Conversely, overexpression of TM in HepJ5 cells decreased metastatic ability. We investigated the possible mechanism and found that decreased TM-mediated enhancement of cell migration was dependent on upregulation of ZEB1, a repressor of E-...Continue Reading

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Citations

Jul 25, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Cheng-Jeng TaiPo-Li Wei
Sep 10, 2014·BioMed Research International·Thian-Sze WongJimmy Yu-Wai Chan
May 18, 2011·Annals of Surgical Oncology·Yan-Ming ZhouJia-Mei Yang
Mar 13, 2012·Cancer Letters·Mario MenschikowskiGabriele Siegert
Mar 19, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chun-Te WuHui-Hsiung Liu
Jul 23, 2013·Journal of Gynecologic Oncology·Yi-Cun ZhongWei-Ping Li
Feb 15, 2018·Journal of Biomedical Science·Vincent Chunpeng PaiMeei Jyh Jiang
May 7, 2019·Cancers·Kwei-Yan LiuShen-Nien Wang

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