title: Cigarette smoke extract induces epithelial-mesenchymal transition of human bladder cancer T24 cells through activation of ERK1/2 pathway.
abstract: Bladder cancer is a common genitourinary malignant disease worldwide. Abundant evidence has shown that cigarette smoke (CS) is a crucial risk factor for bladder cancer. Nevertheless, the mechanism underlying the relationship between cigarette smoking and bladder cancer remains unclear. In the present study, we investigated the effects of cigarette smoke extract (CSE) on mitogen-activated protein kinase (MAPK) pathway activation and EMT alterations in human bladder cancer T24 cells, and the preventive effect of extracellular regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126 was further examined. Our results illustrated that CSE exposure induced morphological change of human bladder cancer T24 cells, enhanced migratory and invasive capacities, reduced epithelial marker expression and elevated mesenchymal marker expression. Meanwhile, exposure of T24 cells to CSE resulted in activation of ERK1/2 pathway as well as activator protein 1 (AP-1) proteins. Interestingly, treatment with ERK1/2 inhibitor U0126 effectively abrogated CSE-triggered EMT and ERK1/2/AP-1 activation. These findings provide novel insight into the molecular mechanisms of CS-associated bladder cancer and may open up new avenues in the search for potential target of bladder cancer intervention.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Urology, Anhui Provincial Children's Hospital, 39 East Wangjiang Road, Hefei, Anhui 230032, PR China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China.
authors.forename: Zhiqi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Anhui International Travel Health Care Center, Anhui Entry-Exit Inspection and Quarantine Bureau, 329 Tunxi Road, Hefei, Anhui 230022, PR China.
authors.forename: Qirui
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China.
authors.forename: Jiaxing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China.
authors.forename: Daming
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, 80 Feicui Rd, Hefei, Anhui 230032, PR China. Electronic address: yudx_urology@126.com.
authors.forename: Dexin
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 818 East Tianyuan Road, Nanjing, Jiangsu 211166, PR China. Electronic address: cyzhong@njmu.edu.cn.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
mesh_terms: D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana / Q000009:adverse effects*; D018808:Transcription Factor AP-1 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000235:genetics
chemical_list: D012906:Smoke; D018808:Transcription Factor AP-1
keywords: AP-1; Bladder cancer; Cigarette smoke extract; ERK1/2; Epithelial–mesenchymal transition