Metadherin promotes hepatocellular carcinoma metastasis through induction of epithelial-mesenchymal transition.
Clin Cancer Res
; 17(23): 7294-302, 2011 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-21976539
ABSTRACT
PURPOSE:
To investigate the expression of metadherin (MTDH) for its prognostic value in hepatocellular carcinoma (HCC) and its role in promoting HCC metastasis. EXPERIMENTALDESIGN:
This study employed a tissue microarray containing samples from 323 HCC patients to examine the expression of MTDH and its correlation with other clinicopathologic characteristics. The role of MTDH in the regulation of HCC metastasis was investigated both in vitro and in vivo using short hairpin RNA (shRNA)-mediated downregulation of MTDH in HCC cell lines with various metastatic potentials.RESULTS:
The expression of MTDH was markedly higher in HCC tumors than in normal liver tissue. Particularly high MTDH expression was observed in tumors with microvascular invasion, pathologic satellites, poor differentiation, or tumor-node-metastasis stages II to III. Furthermore, the clinical outcome was consistently poorer for the MTDH(high) group than for the MTDH(low) group in the 1-, 3-, and 5-year overall survival (OS) rates and in the 1-, 3-, 5-year cumulative recurrence rates. In a nude mice model, the shRNA-mediated downregulation of MTDH resulted in a reduced migratory capacity in HCC cell lines, as well as a reduction in pulmonary and abdominal metastasis. Furthermore, we found that the expression level of MTDH correlated with four epithelial-mesenchymal transition (EMT) markers. Knockdown of MTDH expression in HCC cell lines resulted in downregulation of N-cadherin and snail, upregulation of E-cadherin, and translocation of ß-catenin.CONCLUSIONS:
MTDH may promote HCC metastasis through the induction of EMT process and may be a candidate biomarker for prognosis as well as a target for therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Moléculas de Adhesión Celular
/
Carcinoma Hepatocelular
/
Transición Epitelial-Mesenquimal
/
Neoplasias Hepáticas
/
Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
Límite:
Aged80
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
País de afiliación:
China