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WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance
Zheng, Hongping1; Shao, Fangyuan2; Martin, Scots3; Xu, Xiaoling2; Deng, Chu-Xia1,2
2017-03-06
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Abstract

Cisplatin is one of the most commonly used therapeutic drugs for cancer therapy, yet prolonged cisplatin treatment frequently results in drug resistance. To enhance therapeutic effect of cisplatin, we conducted a high throughput screening using a kinase library containing 704 kinases against triple negative breast cancer (TNBC) cells. We demonstrated that cisplatin activates ATR, CHK1 and WEE1, which shut down DNA replication and attenuate cisplatin induced-lethality. WEE1 inhibition sensitizes TNBCs and cisplatin resistant cancer cells to cisplatin-induced lethality, because it not only impairs DNA replication checkpoint more profoundly than inhibition of ATR or CHK1, but also defects G2-M cell cycle checkpoint. Finally, we demonstrated that combined cisplatin treatment and WEE1 inhibition synergistically inhibits xenograft cancer growth accompanied by markedly reduced expression of TNBC signature genes. Thus targeting DNA replication and G2-M cell cycle checkpoint simultaneously by cisplatin and WEE1 inhibition is promising for TNBCs treatment, and for overcoming their cisplatin resistance.

DOIhttp://doi.org/10.1038/srep43517
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000395429100001
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:15   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorDeng, Chu-Xia
Affiliation1.Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA
2.Faculty of Health Sciences, University of Macau, Macau SAR, China
3.Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, USA
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Zheng, Hongping,Shao, Fangyuan,Martin, Scots,et al. WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance[J]. SCIENTIFIC REPORTS,2017,7.
APA Zheng, Hongping,Shao, Fangyuan,Martin, Scots,Xu, Xiaoling,&Deng, Chu-Xia.(2017).WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance.SCIENTIFIC REPORTS,7.
MLA Zheng, Hongping,et al."WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance".SCIENTIFIC REPORTS 7(2017).
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