Cdc6 Contributes to Cisplatin-resistance by Activation of ATR-Chk1 Pathway in Bladder Cancer Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Jun 2

PMID 27246979

Citations 33

Authors

Sansan Chen

Xinglu Chen

Guie Xie

Yue He

Daoyu Yan

Dianpeng Zheng

Shi Li

Xinyang Fu

Yeping Li

Xiang Pang

Zhiming Hu

Hongwei Li

Wanlong Tan

Jinlong Li

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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