title: EGCG Suppresses ERK5 Activation to Reverse Tobacco Smoke-Triggered Gastric Epithelial-Mesenchymal Transition in BALB/c Mice.
abstract: Tobacco smoke is an important risk factor of gastric cancer. Epithelial-mesenchymal transition is a crucial pathophysiological process in cancer development. ERK5 regulation of epithelial-mesenchymal transition may be sensitive to cell types and/or the cellular microenvironment and its role in the epithelial-mesenchymal transition process remain elusive. Epigallocatechin-3-gallate (EGCG) is a promising chemopreventive agent for several types of cancers. In the present study we investigated the regulatory role of ERK5 in tobacco smoke-induced epithelial-mesenchymal transition in the stomach of mice and the preventive effect of EGCG. Exposure of mice to tobacco smoke for 12 weeks reduced expression of epithelial markers E-cadherin, ZO-1, and CK5, while the expression of mesenchymal markers Snail-1, Vimentin, and N-cadherin were increased. Importantly, we demonstrated that ERK5 modulated tobacco smoke-mediated epithelial-mesenchymal transition in mice stomach, as evidenced by the findings that tobacco smoke elevated ERK5 activation, and that tobacco smoke-triggered epithelial-mesenchymal transition was reversed by ERK5 inhibition. Treatment of EGCG (100 mg/kg BW) effectively attenuated tobacco smoke-triggered activation of ERK5 and epithelial-mesenchymal transition alterations in mice stomach. Collectively, these data suggested that ERK5 was required for tobacco smoke-triggered gastric epithelial-mesenchymal transition and that EGCG suppressed ERK5 activation to reverse tobacco smoke-triggered gastric epithelial-mesenchymal transition in BALB/c mice. These findings provide new insights into the mechanism of tobacco smoke-associated gastric tumorigenesis and the chemoprevention of tobacco smoke-associated gastric cancer.
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. lu_ling60@sina.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. lengyuing@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. zjfyeb@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. bai_ling1234@126.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Bai
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. lucn816@163.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Lu
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. m17705286156@163.com.
authors.forename: Kehuan
authors.initials: K
authors.lastname: Wang
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. limanli123@126.com.
authors.forename: Manli
authors.initials: M
authors.lastname: Li
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. 18752970933@163.com.
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. m17705286167_1@163.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. w871647946@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang 212013, China. jamesnone@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Zhenjiang Matemity and Child Health Care Hospital, Zhenjiang 212001, China. 13862451566@163.com.
authors.forename: Longtao
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Preventive Medicine and Public Health Laboratory Sciences, School of Medicine, Jiangsu University, Zhenjiang 212013, China. liangzhaofeng@ujs.edu.cn.|Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China. liangzhaofeng@ujs.edu.cn.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D048054:Mitogen-Activated Protein Kinase 7 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011897:Random Allocation; D012907:Smoking / Q000009:adverse effects*; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D016588:Anticarcinogenic Agents; D001570:Benzodiazepinones; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C568790:XMD 8-92; D002392:Catechin; C045651:epigallocatechin gallate; D048054:Mitogen-Activated Protein Kinase 7
keywords: EGCG; ERK5; epithelial-mesenchymal transition; gastric cancer; tobacco smoke