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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2010

01-12-2010 | Translational Research and Biomarkers

Knockdown of Thrombomodulin Enhances HCC Cell Migration through Increase of ZEB1 and Decrease of E-cadherin Gene Expression

Authors: Ming-Te Huang, MD, Po-Li Wei, PhD, Jun-Jen Liu, PhD, Der-Zen Liu, PhD, Huang Huey-Chun, PhD, Jane An, BS, Cheng-Chia Wu, BS, Chih-Hsiung Wu, PhD, Yuan-Soon Ho, PhD, Yi-Yuan Yang, PhD, Yu-Jia Chang, PhD

Published in: Annals of Surgical Oncology | Issue 12/2010

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Abstract

Background

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.

Methods

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.

Results

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-cadherin.

Conclusions

TM may be a modulator of cancer metastasis in HCC. Downregulation of TM expression may increase ZEB1 and decrease E-cadherin levels.
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Metadata
Title
Knockdown of Thrombomodulin Enhances HCC Cell Migration through Increase of ZEB1 and Decrease of E-cadherin Gene Expression
Authors
Ming-Te Huang, MD
Po-Li Wei, PhD
Jun-Jen Liu, PhD
Der-Zen Liu, PhD
Huang Huey-Chun, PhD
Jane An, BS
Cheng-Chia Wu, BS
Chih-Hsiung Wu, PhD
Yuan-Soon Ho, PhD
Yi-Yuan Yang, PhD
Yu-Jia Chang, PhD
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 12/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1163-4

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