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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
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.
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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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