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Gap junction protein connexin43 deregulation contributes to bladder carcinogenesis via targeting MAPK pathway

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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.

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Funding

This work was supported by grants from the scientific research youth fund project of affiliated hospital of Chengde medical University.

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    Authors and Affiliations

    1. Department of Urology, Affiliated Hospital of Chengde Medical University, Chengde, China

      Xiao-lin Ai, Qiang Chi, Yu Qiu, Hong-yang Li, Dong-jie Li & Zhi-yong Wang

    2. Department of Pathology, Affiliated Hospital of Chengde Medical University, Chengde, China

      Jia-xu Wang

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    1. Xiao-lin Ai
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    2. Qiang Chi
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    4. Hong-yang Li
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    Correspondence to Zhi-yong Wang.

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    Xiao-lin Ai and Qiang Chi have contributed equally to this work.

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    Ai, Xl., Chi, Q., Qiu, Y. et al. Gap junction protein connexin43 deregulation contributes to bladder carcinogenesis via targeting MAPK pathway. Mol Cell Biochem 428, 109–118 (2017). https://doi.org/10.1007/s11010-016-2921-9

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