期刊
CANCER CELL
卷 28, 期 1, 页码 129-140出版社
CELL PRESS
DOI: 10.1016/j.ccell.2015.06.001
关键词
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资金
- Genomic Technologies and Bioimaging Core Facilities in the Faculty of Life Sciences
- Cancer Research UK
- Medical Research Council
- Wellcome Trust
- Cancer Research UK Senior Fellowship
- Cancer Research UK [11913] Funding Source: researchfish
- Cancer Research UK
- Versus Arthritis [21139] Funding Source: researchfish
- Medical Research Council [MR/L011840/1, MR/L006839/1] Funding Source: researchfish
- MRC [MR/L011840/1, MR/L006839/1] Funding Source: UKRI
Taxol and other antimitotic agents are frontline chemotherapy agents but the mechanisms responsible for patient benefit remain unclear. Following a genome-wide siRNA screen, we identified the oncogenic transcription factor Myc as a taxol sensitizer. Using time-lapse imaging to correlate mitotic behavior with cell fate, we show that Myc sensitizes cells to mitotic blockers and agents that accelerate mitotic progression. Myc achieves this by upregulating a cluster of redundant pro-apoptotic BH3-only proteins and suppressing pro-survival Bcl-xL. Gene expression analysis of breast cancers indicates that taxane responses correlate positively with Myc and negatively with Bcl-xL. Accordingly, pharmacological inhibition of Bcl-xL restores apoptosis in Myc-deficient cells. These results open up opportunities for biomarkers and combination therapies that could enhance traditional and second-generation antimitotic agents.
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