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Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477574/ https://www.ncbi.nlm.nih.gov/pubmed/28383563 http://dx.doi.org/10.1038/cddis.2017.126 |
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author | Han, Jihua Xie, Changming Pei, Tiemin Wang, Jiabei Lan, Yaliang Huang, Kaihua Cui, Yifeng Wang, Fengyue Zhang, Jiewu Pan, Shangha Liang, Yingjian Zhen, Tongsen Song, Ruipeng Sun, Boshi Li, Yuejin Shi, Huawen Yang, Guangchao Liu, Xirui Zhu, Mingxi Wang, Yan Li, Keyu Liu, Yao Meng, Fanzheng Liao, Fei Meng, Xianzhi Hong, Xuehui Liu, Lianxin |
author_facet | Han, Jihua Xie, Changming Pei, Tiemin Wang, Jiabei Lan, Yaliang Huang, Kaihua Cui, Yifeng Wang, Fengyue Zhang, Jiewu Pan, Shangha Liang, Yingjian Zhen, Tongsen Song, Ruipeng Sun, Boshi Li, Yuejin Shi, Huawen Yang, Guangchao Liu, Xirui Zhu, Mingxi Wang, Yan Li, Keyu Liu, Yao Meng, Fanzheng Liao, Fei Meng, Xianzhi Hong, Xuehui Liu, Lianxin |
author_sort | Han, Jihua |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5477574 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-54775742017-07-03 Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis Han, Jihua Xie, Changming Pei, Tiemin Wang, Jiabei Lan, Yaliang Huang, Kaihua Cui, Yifeng Wang, Fengyue Zhang, Jiewu Pan, Shangha Liang, Yingjian Zhen, Tongsen Song, Ruipeng Sun, Boshi Li, Yuejin Shi, Huawen Yang, Guangchao Liu, Xirui Zhu, Mingxi Wang, Yan Li, Keyu Liu, Yao Meng, Fanzheng Liao, Fei Meng, Xianzhi Hong, Xuehui Liu, Lianxin Cell Death Dis Original Article 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. Nature Publishing Group 2017-04 2017-04-06 /pmc/articles/PMC5477574/ /pubmed/28383563 http://dx.doi.org/10.1038/cddis.2017.126 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Original Article Han, Jihua Xie, Changming Pei, Tiemin Wang, Jiabei Lan, Yaliang Huang, Kaihua Cui, Yifeng Wang, Fengyue Zhang, Jiewu Pan, Shangha Liang, Yingjian Zhen, Tongsen Song, Ruipeng Sun, Boshi Li, Yuejin Shi, Huawen Yang, Guangchao Liu, Xirui Zhu, Mingxi Wang, Yan Li, Keyu Liu, Yao Meng, Fanzheng Liao, Fei Meng, Xianzhi Hong, Xuehui Liu, Lianxin Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis |
title | Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis |
title_full | Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis |
title_fullStr | Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis |
title_full_unstemmed | Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis |
title_short | Deregulated AJAP1/β-catenin/ZEB1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis |
title_sort | deregulated ajap1/β-catenin/zeb1 signaling promotes hepatocellular carcinoma carcinogenesis and metastasis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5477574/ https://www.ncbi.nlm.nih.gov/pubmed/28383563 http://dx.doi.org/10.1038/cddis.2017.126 |
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