The tumor suppressor DLC1 inhibits cancer progression and oncogenic autophagy in hepatocellular carcinoma.
Lab Invest
; 98(8): 1014-1024, 2018 08.
Article
en En
| MEDLINE
| ID: mdl-29785050
ABSTRACT
Downregulation of deleted in liver cancer 1 (DLC1) is associated with poor prognosis of various cancers, but its functional mechanisms in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the roles of DLC1 in tumor progression and autophagy of HCC. We found that DLC1 was frequently downregulated in HCC tissues. Underexpression of DLC1 correlated with AFP level, vascular invasion, poor differentiation, and poor prognosis. In vitro assays revealed that DLC1 not only suppressed the proliferation, migration, and invasion of HCC cells, but also inhibited autophagy of HCC cells. Mechanistic investigation revealed that DLC1 decreased TCF4 expression and the interaction between ß-catenin and TCF4, then inactivated Wnt/ß-catenin signaling. Additionally, DLC1 suppressed the ROCK1 activity and the dissociation of the Beclin1-Bcl2 complex, thereby inhibiting autophagy of HCC cells. In conclusion, our findings imply that loss of DLC1 contributes to the progression and oncogenic autophagy of HCC.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
/
Regulación Neoplásica de la Expresión Génica
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Carcinoma Hepatocelular
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Proteínas Activadoras de GTPasa
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Proteínas Supresoras de Tumor
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Neoplasias Hepáticas
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Lab Invest
Año:
2018
Tipo del documento:
Article
País de afiliación:
China