Cdc6 contributes to cisplatin-resistance by activation of ATR-Chk1 pathway in bladder cancer cells
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Sansan Chen1,2,*, Xinglu Chen2,*, Gui’e Xie3,*, Yue He2, Daoyu Yan2, Dianpeng Zheng2, Shi Li1, Xinyang Fu1, Yeping Li1, Xiang Pang1, Zhiming Hu2, Hongwei Li2, Wanlong Tan1, Jinlong Li2
1Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
2Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
3KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong, China
*These authors contributed equally to this work
Jinlong Li, email: email@example.com
Wanlong Tan, email: firstname.lastname@example.org
Hongwei Li, email: email@example.com
Keywords: Cdc6, ATR, cisplatin-resistance, bladder cancer
Received: January 07, 2016 Accepted: May 08, 2016 Published: May 26, 2016
High activation of DNA damage response is implicated in cisplatin (CDDP) resistance which presents as a serious obstacle for bladder cancer treatment. Cdc6 plays an important role in the malignant progression of tumor. Here, we reported that Cdc6 expression is up-regulated in bladder cancer tissues and is positively correlated to high tumor grade. Cdc6 depletion can attenuate the malignant properties of bladder cancer cells, including DNA replication, migration and invasion. Furthermore, higher levels of chromatin-binding Cdc6 and ATR were detected in CDDP-resistant bladder cancer cells than in the parent bladder cancer cells. Intriguingly, down-regulation of Cdc6 can enhance sensitivity to CDDP both in bladder cancer cells and CDDP-resistant bladder cancer cells. Cdc6 depletion abrogates S phase arrest caused by CDDP, leading to aberrant mitosis by inactivating ATR-Chk1-Cdc25C pathway. Our results indicate that Cdc6 may be a promising target for overcoming CDDP resistance in bladder cancer.
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