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ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition

As the primary cause of lung cancer, tobacco smoke (TS) promotes the initiation and progression of lung tumorigenesis. Epithelial-mesenchymal transition (EMT) is a crucial process involved in cell malignant transformation. The role of ERK5, the lesser studied member of MAPKs family, in regulating TS...

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Autores principales: Liang, Zhaofeng, Xie, Wei, Wu, Rui, Geng, Hao, Zhao, Li, Xie, Chunfeng, Li, Xiaoting, Huang, Cong, Zhu, Jianyun, Zhu, Mingming, Zhu, Weiwei, Wu, Jieshu, Geng, Shanshan, Zhong, Caiyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637308/
https://www.ncbi.nlm.nih.gov/pubmed/25965818
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author Liang, Zhaofeng
Xie, Wei
Wu, Rui
Geng, Hao
Zhao, Li
Xie, Chunfeng
Li, Xiaoting
Huang, Cong
Zhu, Jianyun
Zhu, Mingming
Zhu, Weiwei
Wu, Jieshu
Geng, Shanshan
Zhong, Caiyun
author_facet Liang, Zhaofeng
Xie, Wei
Wu, Rui
Geng, Hao
Zhao, Li
Xie, Chunfeng
Li, Xiaoting
Huang, Cong
Zhu, Jianyun
Zhu, Mingming
Zhu, Weiwei
Wu, Jieshu
Geng, Shanshan
Zhong, Caiyun
author_sort Liang, Zhaofeng
collection PubMed
description As the primary cause of lung cancer, tobacco smoke (TS) promotes the initiation and progression of lung tumorigenesis. Epithelial-mesenchymal transition (EMT) is a crucial process involved in cell malignant transformation. The role of ERK5, the lesser studied member of MAPKs family, in regulating TS-triggered pulmonary EMT has not been investigated. Normal human bronchial epithelial cells and BALB/c mice were used as in vitro and in vivo TS exposure models. Exposure of normal human bronchial epithelial cells to TS for 7 days induced morphological change, enhanced migratory and invasive capacities, reduced epithelial marker expression and increased mesenchymal marker expression. Importantly, we demonstrated for the first time that ERK5 negatively regulated TS-mediated lung epithelial EMT, as evidenced by the findings that TS suppressed ERK5 activation, and that TS-triggered EMT was mimicked with ERK5 inhibition and reversed by ERK5 overexpression. The negative regulation of ERK5 on pulmonary EMT was further confirmed in mice exposed to TS for 12 weeks. Taken together, our data suggest that ERK5 negatively regulates TS-mediated pulmonary EMT. These findings provide new insight into the molecular mechanisms of TS-associated lung tumorigenesis and may open up new avenues in the search for potential target of lung cancer intervention.
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spelling pubmed-46373082015-12-02 ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition Liang, Zhaofeng Xie, Wei Wu, Rui Geng, Hao Zhao, Li Xie, Chunfeng Li, Xiaoting Huang, Cong Zhu, Jianyun Zhu, Mingming Zhu, Weiwei Wu, Jieshu Geng, Shanshan Zhong, Caiyun Oncotarget Research Paper As the primary cause of lung cancer, tobacco smoke (TS) promotes the initiation and progression of lung tumorigenesis. Epithelial-mesenchymal transition (EMT) is a crucial process involved in cell malignant transformation. The role of ERK5, the lesser studied member of MAPKs family, in regulating TS-triggered pulmonary EMT has not been investigated. Normal human bronchial epithelial cells and BALB/c mice were used as in vitro and in vivo TS exposure models. Exposure of normal human bronchial epithelial cells to TS for 7 days induced morphological change, enhanced migratory and invasive capacities, reduced epithelial marker expression and increased mesenchymal marker expression. Importantly, we demonstrated for the first time that ERK5 negatively regulated TS-mediated lung epithelial EMT, as evidenced by the findings that TS suppressed ERK5 activation, and that TS-triggered EMT was mimicked with ERK5 inhibition and reversed by ERK5 overexpression. The negative regulation of ERK5 on pulmonary EMT was further confirmed in mice exposed to TS for 12 weeks. Taken together, our data suggest that ERK5 negatively regulates TS-mediated pulmonary EMT. These findings provide new insight into the molecular mechanisms of TS-associated lung tumorigenesis and may open up new avenues in the search for potential target of lung cancer intervention. Impact Journals LLC 2015-04-17 /pmc/articles/PMC4637308/ /pubmed/25965818 Text en Copyright: © 2015 Liang 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
Liang, Zhaofeng
Xie, Wei
Wu, Rui
Geng, Hao
Zhao, Li
Xie, Chunfeng
Li, Xiaoting
Huang, Cong
Zhu, Jianyun
Zhu, Mingming
Zhu, Weiwei
Wu, Jieshu
Geng, Shanshan
Zhong, Caiyun
ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
title ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
title_full ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
title_fullStr ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
title_full_unstemmed ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
title_short ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
title_sort erk5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4637308/
https://www.ncbi.nlm.nih.gov/pubmed/25965818
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