title: Gap junction protein connexin43 deregulation contributes to bladder carcinogenesis via targeting MAPK pathway.
abstract: High expression of connexins was found in a variety of cancers, but their role is still controversial. We investigated whether connexin43 (Cx43) contributed to bladder carcinogenesis through MAPK activation. In this study, we found that Cx43 expression was significantly increased in bladder cancer tissues and cell line. Overexpression of Cx43 in bladder cancer 5637 cells increased cell proliferation, promoted cell cycle progression, and inhibited apoptosis. Western blot showed that JNK and ERK pathways were dramatically activated in Cx43-overexpressed cells. Conversely, knockdown of Cx43 inhibited cell proliferation by increasing apoptosis and causing cell cycle arrest, concomitant with inhibition of JNK and ERK signaling. In addition, JNK and ERK pathways were also activated in bladder cancer tissues. In conclusion, abnormal high expression and cytoplasmic localization of Cx43 contributed to bladder cancer. Inhibition of Cx43 activity could be a potential therapeutic strategy for preventing the progression of bladder cancer.
authors.affiliation: Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Ai
authors.affiliation: Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chi
authors.affiliation: Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde, China.
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde, China.
authors.forename: Dong-Jie
authors.initials: DJ
authors.lastname: Li
authors.affiliation: Department of Pathology, Affiliated Hospital of Chengde Medical University, Chengde, China.
authors.forename: Jia-Xu
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde, China. wangzhiyong2863@outlook.com.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human
keywords: Bladder cancer; Connexin43; ERK; JNK