title: ERK5 negatively regulates tobacco smoke-induced pulmonary epithelial-mesenchymal transition.
abstract: 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.
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Anhui Medical University, Anhui, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Surgery, The Second Affiliated Hospital of Anhui Medical University, Anhui, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jieshu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Geng
authors.affiliation: Department of Toxicology and Nutritional Science, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008175:Lung Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014162:Transfection
chemical_list: D047428:Protein Kinase Inhibitors; D012906:Smoke; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7
keywords: ERK5; epithelial–mesenchymal transition; lung cancer; regulation; tobacco smoke