Glucose-regulated protein 94 mediates cancer progression via AKT and eNOS in hepatocellular carcinoma.
Tumour Biol
; 37(4): 4295-304, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26493996
ABSTRACT
Hepatocellular carcinoma (HCC) is a crucial health issue worldwide. High glucose-regulated protein 94 (GRP94) expression has been observed in different types of cancer, suggesting a link between tumor progression and GRP94 expression. However, the mechanisms underlying the role of GRP94 in HCC progression remain unclear. We used specific small hairpin RNA (shRNA) to manipulate GRP94 expression in HCC cells. Tissue arrays, MTT assays, xCELLigence assays, and in vivo xenograft model were performed to identify clinicopathological correlations and to analyze cell growth. We found that high GRP94 expression reflected a poor response and a lower survival rate. In vitro and in vivo studies showed that silencing GRP94 suppressed cancer progression. Mechanistically, GRP94 knockdown reduced AKT, phospho-AKT, and eNOS levels but did not influence the AMPK pathway. Our results demonstrated that GRP94 is a key molecule in HCC progression that modulates the AKT pathway and eNOS levels. Our findings suggest that GRP94 may be a new prognostic and therapeutic target for HCC.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
/
Carcinoma Hepatocelular
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Óxido Nítrico Sintase Tipo III
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Proteínas Proto-Oncogênicas c-akt
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Tumour Biol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Taiwan