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Cell Death Dis ; 8(4): e2736, 2017 04 06.
Article in English | 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.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Cell Adhesion Molecules/biosynthesis , Liver Neoplasms/metabolism , Neoplasm Proteins/biosynthesis , Signal Transduction , Zinc Finger E-box-Binding Homeobox 1/biosynthesis , beta Catenin/biosynthesis , Active Transport, Cell Nucleus/genetics , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Nucleus/genetics , Cell Nucleus/metabolism , Cell Nucleus/pathology , Epithelial-Mesenchymal Transition/genetics , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Metastasis , Neoplasm Proteins/genetics , Transcription, Genetic , Zinc Finger E-box-Binding Homeobox 1/genetics , beta Catenin/genetics
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