DESCRIPTION:

Kinases that when silenced confer sensitivity of MDA-MG-231 cells to cisplatin. All gene symbols were mapped to HGNC identifiers.

LABEL:

WEE1-cisplatin resistance

SCORE TYPE:

Binary

DATE ADDED:

2017-05-09

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Zheng H, Shao F, Martin S, Xu X, Deng CX

TITLE:

WEE1 inhibition targets cell cycle checkpoints for triple negative breast cancers to overcome cisplatin resistance.

JOURNAL:

Scientific reports Mar 2017, Vol 7, pp. 43517

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. PUBMED: 28262781
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