期刊
CELL REPORTS
卷 28, 期 9, 页码 2345-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.07.070
关键词
-
类别
资金
- Netherlands Organization for Scientific Research [NWO-VIDI 916-76062]
- European Research Council [ERC CoG 682421]
- Dutch Cancer Society [RUG 2011-5093]
- Rene Vogels Foundation
- De Boer-Merema Foundation
- American Cancer Society [RSG-17-011-01]
- NIGMS/NIH [R01GM127559]
- Translational Cancer Biology Training Grant [T32-CA130807]
Triple-negative breast cancers (TNBCs) display great diversity in cisplatin sensitivity that cannot be explained solely by cancer-associated DNA repair defects. Differential activation of the DNA damage response (DDR) to cisplatin has been proposed to underlie the observed differential sensitivity, but it has not been investigated systematically. Systems-level analysis-using quantitative time-resolved signaling data and phenotypic responses, in combination with mathematical modeling-identifies that the activation status of cell-cycle checkpoints determines cisplatin sensitivity in TNBC cell lines. Specifically, inactivation of the cell-cycle checkpoint regulator MK2 or G3BP2 sensitizes cisplatin-resistant TNBC cell lines to cisplatin. Dynamic signaling data of five cell cycle-related signals predicts cisplatin sensitivity of TNBC cell lines. We provide a time-resolved map of cisplatin-induced signaling that uncovers determinants of chemo-sensitivity, underscores the impact of cell-cycle checkpoints on cisplatin sensitivity, and offers starting points to optimize treatment efficacy.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据