title: Cigarette smoke induced urocystic epithelial mesenchymal transition via MAPK pathways.
abstract: Cigarette smoke has been shown to be a major risk factor for bladder cancer. Epithelial-mesenchymal transition (EMT) is a crucial process in cancer development. The role of MAPK pathways in regulating cigarette smoke-triggered urocystic EMT remains to be elucidated. Human normal urothelial cells and BALB/c mice were used as in vitro and in vivo cigarette smoke exposure models. Exposure of human normal urothelial cells to cigarette smoke induced morphological change, enhanced migratory and invasive capacities, reduced epithelial marker expression and increased mesenchymal marker expression, along with the activation of MAPK pathways. Moreover, we revealed that ERK1/2 and p38 inhibitors, but rather JNK inhibitor, effectively attenuated cigarette smoke-induced urocystic EMT. Importantly, the regulatory function of ERK1/2 and p38 pathways in cigarette smoke-triggered urocystic EMT was further confirmed in mice exposed to CS for 12 weeks. These findings could provide new insight into the molecular mechanisms of cigarette smoke-associated bladder cancer development as well as its potential intervention.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Jiangsu 212013, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Min
authors.affiliation: Department of Toxicology and Nutritional Science, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D000073865:Cigarette Smoking / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D019570:Inhalation Exposure; D008297:Male; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction; D012906:Smoke / Q000009:adverse effects*; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D019459:Urothelium / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D012906:Smoke; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: MAPK pathways; bladder cancer; cigarette smoke; epithelial mesenchymal transition