机构：[1]Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, Shenzhen, Guangdong 518122[2]Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou,[3]The Third Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006[4]Department of Vascular Surgery, The Third Affiliated Hospital, Southern Medical University[5]Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China中山大学附属第三医院
Bladder cancer is a common tumor type of the urinary system, which has high levels of morbidity and mortality. The first-line treatment is cisplatin-based combination chemotherapy, but a significant proportion of patients relapse due to the development of drug resistance. Therapy-induced senescence can act as a 'back-up' response to chemotherapy in cancer types that are resistant to apoptosis-based anticancer therapies. The circadian clock serves an important role in drug resistance and cellular senescence. The aim of the present study was to investigate the regulatory effect of the circadian clock on paclitaxel (PTX)-induced senescence in cisplatin-resistant bladder cancer cells. Cisplatin-resistant bladder cancer cells were established via long-term cisplatin incubation. PTX induced apparent senescence in bladder cancer cells as demonstrated via SA-beta-Gal staining, but this was not observed in the cisplatin-resistant cells. The cisplatin-resistant cells entered into a quiescent state with prolonged circadian rhythm under acute PTX stress. It was identified that the circadian protein cryptochrome1 (CRY1) accumulated in these quiescent cisplatin-resistant cells, and that CRY1 knockdown restored PTX-induced senescence. Mechanistically, CRY1 promoted p53 degradation via increasing the binding of p53 with its ubiquitin E3 ligase MDM2 proto-oncogene. These data suggested that the accumulated CRY1 in cisplatin-resistant cells could prevent PTX-induced senescence by promoting p53 degradation.
基金：
Shenzhen Science and Technology Project [JCYJ20180305 164655077, JCYJ20180305124227251]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81672915]
第一作者机构：[1]Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, Shenzhen, Guangdong 518122[2]Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou,
通讯作者：
通讯机构：[1]Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, Shenzhen, Guangdong 518122[2]Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou,[5]Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China[*1]Shenzhen Ruipuxun Academy for Stem Cell and Regenerative Medicine, 14 Jinhui Road, Shenzhen, Guangdong 518122, P.R. China
推荐引用方式(GB/T 7714)：
Jia Min,Su Bijia,Mo Lijun,et al.Circadian clock protein CRY1 prevents paclitaxel-induced senescence of bladder cancer cells by promoting p53 degradation[J].ONCOLOGY REPORTS.2021,45(3):1033-1043.doi:10.3892/or.2020.7914.
APA：
Jia, Min,Su, Bijia,Mo, Lijun,Qiu, Wen,Ying, Jiaxu...&Li, Jinlong.(2021).Circadian clock protein CRY1 prevents paclitaxel-induced senescence of bladder cancer cells by promoting p53 degradation.ONCOLOGY REPORTS,45,(3)
MLA：
Jia, Min,et al."Circadian clock protein CRY1 prevents paclitaxel-induced senescence of bladder cancer cells by promoting p53 degradation".ONCOLOGY REPORTS 45..3(2021):1033-1043
