Deregulated AJAP1/ß-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis.
Cell Death Dis
; 8(4): e2736, 2017 04 06.
Article
em En
| MEDLINE
| ID: mdl-28383563
ABSTRACT
Adherens junctions-associated protein 1 (AJAP1) is an integral membrane protein that is thought to function as a tumor suppressor in various malignancies. Downregulation of AJAP1 mRNA levels may predict recurrence in hepatocellular carcinoma (HCC) patients, but the underlying molecular mechanism is unknown. This was addressed in the present study by examining the role of AJAP1 in HCC cell proliferation, migration, and invasion in vitro as well as in human specimens and mouse xenograft model. We found that AJAP1 expression was reduced in HCC cells and human HCC tissue, which was associated with metastasis. AJAP1 overexpression inhibited HCC progression and metastasis, while its silencing had the opposite effect both in vitro and in vivo. Furthermore, AJAP1 blocked epithelial-to-mesenchymal transition by interacting with ß-catenin and inhibiting its nuclear translocation, which suppressed zinc finger E-box binding homeobox 1 (ZEB1) transcription. These results indicate that AJAP1 inhibits HCC metastasis, and is thus a potential therapeutic target for HCC treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Moléculas de Adesão Celular
/
Carcinoma Hepatocelular
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Beta Catenina
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Homeobox 1 de Ligação a E-box em Dedo de Zinco
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Neoplasias Hepáticas
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China