Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis
Autor: | Fanzheng Meng, Jiewu Zhang, Keyu Li, Fei Liao, Yan Wang, Boshi Sun, Yifeng Cui, Tongsen Zhen, Jihua Han, Fengyue Wang, Yao Liu, Kaihua Huang, Shangha Pan, Changming Xie, Guangchao Yang, Mingxi Zhu, Ruipeng Song, Tiemin Pei, Lianxin Liu, Yingjian Liang, Xirui Liu, Yuejin Li, Huawen Shi, Xianzhi Meng, Yaliang Lan, Xuehui Hong, Jiabei Wang |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Cancer Research Pathology medicine.medical_specialty Beta-catenin Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Transcription Genetic Immunology Active Transport Cell Nucleus Mice Nude Biology medicine.disease_cause Metastasis Adherens junction 03 medical and health sciences Cellular and Molecular Neuroscience Mice 0302 clinical medicine Downregulation and upregulation Cell Line Tumor medicine Gene silencing Animals Humans Epithelial–mesenchymal transition Neoplasm Metastasis beta Catenin Cell Nucleus Mice Inbred BALB C Liver Neoplasms Zinc Finger E-box-Binding Homeobox 1 Cell Biology medicine.disease digestive system diseases Neoplasm Proteins 030104 developmental biology 030220 oncology & carcinogenesis Catenin Cancer research biology.protein Original Article Carcinogenesis Cell Adhesion Molecules Signal Transduction |
Zdroj: | Cell Death & Disease |
ISSN: | 2041-4889 |
Popis: | 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 β-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. |
Databáze: | OpenAIRE |
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