Knockdown of thrombomodulin enhances HCC cell migration through increase of ZEB1 and decrease of E-cadherin gene expression.
Ann Surg Oncol
; 17(12): 3379-85, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20625840
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Caderinas
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Movimento Celular
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Trombomodulina
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Carcinoma Hepatocelular
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Proteínas de Homeodomínio
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Neoplasias Hepáticas
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article