ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial–mesenchymal transition
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Zhaofeng Liang1, Wei Xie1, Rui Wu1, Hao Geng2, Li Zhao2, Chunfeng Xie1, Xiaoting Li1, Cong Huang1, Jianyun Zhu1, Mingming Zhu1, Weiwei Zhu1, Jieshu Wu1, Shanshan Geng1, Caiyun Zhong1,3
1Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China
2Department of Surgery, The Second Affiliated Hospital of Anhui Medical University, Anhui, China
3The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
Caiyun Zhong, e-mail: [email protected]
Keywords: tobacco smoke, lung cancer, ERK5, epithelial–mesenchymal transition, regulation
Received: February 12, 2015 Accepted: April 06, 2015 Published: April 17, 2015
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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