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
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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