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Cell Death Dis ; 8(4): e2736, 2017 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-28383563

RESUMO

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.


Assuntos
Carcinoma Hepatocelular/metabolismo , Moléculas de Adesão Celular/biossíntese , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/biossíntese , Transdução de Sinais , Homeobox 1 de Ligação a E-box em Dedo de Zinco/biossíntese , beta Catenina/biossíntese , Transporte Ativo do Núcleo Celular/genética , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Transição Epitelial-Mesenquimal/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Proteínas de Neoplasias/genética , Transcrição Gênica , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , beta Catenina/genética
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