生物
乳腺癌
癌症研究
异位表达
癌症
顺铂
激酶
癌细胞
蛋白激酶A
细胞生物学
细胞培养
化疗
遗传学
作者
Rong Liu,Guangxi Yang,Min Bao,Zhongmei Zhou,Xiaoyun Mao,Wenjing Liu,Xingming Jiang,Di Zhu,Xinle Ren,Jian Huang,Ceshi Chen
出处
期刊:Oncogene
[Springer Nature]
日期:2022-03-02
卷期号:41 (16): 2265-2274
被引量:9
标识
DOI:10.1038/s41388-022-02252-7
摘要
Dual-specificity mitogen-activated protein kinase phosphatase-1 (MKP-1/DUSP1/CL-100) has been documented to promote breast cancer cell survival and chemoresistance. MKP-1 is an unstable protein that is ubiquitinated and degraded via the ubiquitin-proteasome system. However, it is not clear how MKP-1 protein stability is regulated in breast cancer. In this study, we performed a genome-wide siRNA library screen of deubiquitinases (DUBs) and identified STAMBPL1 as an MKP-1 DUB in breast cancer cells. STAMBPL1 interacts with MKP-1 and stabilizes MKP-1 via deubiquitination. Both STAMBPL1 and MKP-1 depletion sensitize breast cancer cells to cisplatin in vitro and in vivo, and ectopic overexpression of MKP-1 partially rescues STAMBPL1 depletion-induced cisplatin sensitivity. Furthermore, STAMBPL1 and MKP-1 depletion increased breast cancer sensitivity to cisplatin by increasing the phosphorylation and activation of c-Jun N-terminal protein kinase (JNK). Collectively, our findings not only identify STAMBPL1 as an MKP-1 DUB but also reveal a critical mechanism that regulates MKP-1 expression in breast cancer. Our findings indicate that the STAMBPL1/MKP-1 axis represents a potential therapeutic target in breast cancer.
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