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Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC
Protein 4.1N is a member of protein 4.1 family and has been recognized as a potential tumor suppressor in solid tumors. Here, we aimed to investigate the role and mechanisms of 4.1N in non-small cell lung cancer (NSCLC). We confirmed that the expression level of 4.1N was inversely correlated with th...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808014/ https://www.ncbi.nlm.nih.gov/pubmed/26575790 |
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author | Wang, Zi Ma, Bianyin Li, Hui Xiao, Xiaojuan Zhou, Weihua Liu, Feng Zhang, Bin Zhu, Min Yang, Qin Zeng, Yayue Sun, Yang Sun, Shuming Wang, Yanpeng Zhang, Yibin Weng, Haibo Chen, Lixiang Ye, Mao An, Xiuli Liu, Jing |
author_facet | Wang, Zi Ma, Bianyin Li, Hui Xiao, Xiaojuan Zhou, Weihua Liu, Feng Zhang, Bin Zhu, Min Yang, Qin Zeng, Yayue Sun, Yang Sun, Shuming Wang, Yanpeng Zhang, Yibin Weng, Haibo Chen, Lixiang Ye, Mao An, Xiuli Liu, Jing |
author_sort | Wang, Zi |
collection | PubMed |
description | Protein 4.1N is a member of protein 4.1 family and has been recognized as a potential tumor suppressor in solid tumors. Here, we aimed to investigate the role and mechanisms of 4.1N in non-small cell lung cancer (NSCLC). We confirmed that the expression level of 4.1N was inversely correlated with the metastatic properties of NSCLC cell lines and histological grade of clinical NSCLC tissues. Specific knockdown of 4.1N promoted tumor cell proliferation, migration and adhesion in vitro, and tumor growth and metastasis in mouse xenograft models. Furthermore, we identified PP1 as a novel 4.1N-interacting molecule, and the FERM domain of 4.1N mediated the interaction between 4.1N and PP1. Further, ectopic expression of 4.1N could inactivate JNK-c-Jun signaling pathway through enhancing PP1 activity and interaction between PP1 and p-JNK. Correspondingly, expression of potential downstream metastasis targets (ezrin and MMP9) and cell cycle targets (p53, p21 and p19) of JNK-c-Jun pathway were also regulated by 4.1N. Our data suggest that down-regulation of 4.1N expression is a critical step for NSCLC development and that repression of JNK-c-Jun signaling through PP1 is one of the key anti-tumor mechanisms of 4.1N. |
format | Online Article Text |
id | pubmed-4808014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48080142016-04-19 Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC Wang, Zi Ma, Bianyin Li, Hui Xiao, Xiaojuan Zhou, Weihua Liu, Feng Zhang, Bin Zhu, Min Yang, Qin Zeng, Yayue Sun, Yang Sun, Shuming Wang, Yanpeng Zhang, Yibin Weng, Haibo Chen, Lixiang Ye, Mao An, Xiuli Liu, Jing Oncotarget Research Paper Protein 4.1N is a member of protein 4.1 family and has been recognized as a potential tumor suppressor in solid tumors. Here, we aimed to investigate the role and mechanisms of 4.1N in non-small cell lung cancer (NSCLC). We confirmed that the expression level of 4.1N was inversely correlated with the metastatic properties of NSCLC cell lines and histological grade of clinical NSCLC tissues. Specific knockdown of 4.1N promoted tumor cell proliferation, migration and adhesion in vitro, and tumor growth and metastasis in mouse xenograft models. Furthermore, we identified PP1 as a novel 4.1N-interacting molecule, and the FERM domain of 4.1N mediated the interaction between 4.1N and PP1. Further, ectopic expression of 4.1N could inactivate JNK-c-Jun signaling pathway through enhancing PP1 activity and interaction between PP1 and p-JNK. Correspondingly, expression of potential downstream metastasis targets (ezrin and MMP9) and cell cycle targets (p53, p21 and p19) of JNK-c-Jun pathway were also regulated by 4.1N. Our data suggest that down-regulation of 4.1N expression is a critical step for NSCLC development and that repression of JNK-c-Jun signaling through PP1 is one of the key anti-tumor mechanisms of 4.1N. Impact Journals LLC 2015-11-13 /pmc/articles/PMC4808014/ /pubmed/26575790 Text en Copyright: © 2016 Wang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Wang, Zi Ma, Bianyin Li, Hui Xiao, Xiaojuan Zhou, Weihua Liu, Feng Zhang, Bin Zhu, Min Yang, Qin Zeng, Yayue Sun, Yang Sun, Shuming Wang, Yanpeng Zhang, Yibin Weng, Haibo Chen, Lixiang Ye, Mao An, Xiuli Liu, Jing Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC |
title | Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC |
title_full | Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC |
title_fullStr | Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC |
title_full_unstemmed | Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC |
title_short | Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC |
title_sort | protein 4.1n acts as a potential tumor suppressor linking pp1 to jnk-c-jun pathway regulation in nsclc |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4808014/ https://www.ncbi.nlm.nih.gov/pubmed/26575790 |
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