| 论文题目: | STAMBPL1 Promotes Breast Cancer Cell Resistance to Cisplatin Partially by Stabilizing MKP-1 Expression |
| 作者: | Liu, R; Yang, GX; Bao, M; Zhou, ZM; Mao, XY ; Liu, WJ; Jiang, XY; Zhu, D; Ren, XL; Huang, J; Chen, CS |
| 联系作者: | chenc@mail.kiz.ac.cn |
| 发表年度: | 2022 |
| DOI: | DOI10.1038/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 |
| 刊物名称: | Oncogene |
| 论文出处: | https://www.nature.com/articles/s41388-022-02252-7 |
| 影响因子: | 9.867(2020IF) |
