title: ERK5 positively regulates cigarette smoke-induced urocystic epithelial-mesenchymal transition in SV‑40 immortalized human urothelial cells.
abstract: Bladder cancer is universally acknowledged as a significant public health issue. Abundant evidence shows that cigarette smoke (CS) is the primary risk factor for bladder cancer. However, the mechanism of CS-induced bladder cancer has not been fully elucidated. CS-induced epithelial-mesenchymal transition (EMT) is critically involved in cell malignant transformation. The role of ERK5, the lesser studied member of the MAPK family, in regulating CS-triggered EMT has not yet been investigated. The objective of the present study was to investigate the regulatory role of ERK5 in CS-induced urocystic EMT. SV-40 immortalized normal human urothelial cells (SV-HUC-1) were used as in vitro CS exposure models. EMT phenotypic alterations were assessed by changes in cell morphology, invasive capacity, as well as expression of epithelial and mesenchymal markers. Protein and mRNA expression levels were analyzed by western blotting and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). ERK5 inhibition studies were performed with a specific inhibitor. Exposure of SV-HUC-1 cells to CS induced morphological change, enhanced invasive capacity, reduced epithelial marker expression and increased mesenchymal marker expression. Importantly, we demonstrated for the first time that ERK5 positively regulated CS-mediated EMT in urothelial cells, as evidenced by the findings that CS promoted ERK5 activation, and that the CS-triggered alteration in the EMT phenotype was reversed by ERK5 inhibition.
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Geng
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Liangkuan
authors.initials: L
authors.lastname: Bi
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhong
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006801:Humans; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors / Q000235:genetics*; D013539:Simian virus 40 / Q000235:genetics; D012906:Smoke / Q000009:adverse effects; D062789:Tobacco Products / Q000633:toxicity; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology / Q000821:virology; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
chemical_list: D012906:Smoke; D048054:Mitogen-Activated Protein Kinase 7