期刊
CELL
卷 163, 期 1, 页码 174-186出版社
CELL PRESS
DOI: 10.1016/j.cell.2015.08.063
关键词
-
资金
- NIH [R01CA179483-01]
- MIT-DFCI Bridge grant
- NIH/NCI [P50 CA168504]
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that exhibits extremely high levels of genetic complexity and yet a relatively uniform transcriptional program. We postulate that TNBC might be highly dependent on uninterrupted transcription of a key set of genes within this gene expression program and might therefore be exceptionally sensitive to inhibitors of transcription. Utilizing kinase inhibitors and CRISPR/Cas9-mediated gene editing, we show here that triple-negative but not hormone receptor-positive breast cancer cells are exceptionally dependent on CDK7, a transcriptional cyclin-dependent kinase. TNBCcells are unique in their dependence on this transcriptional CDK and suffer apoptotic cell death upon CDK7 inhibition. An Achilles cluster'' of TNBC-specific genes is especially sensitive to CDK7 inhibition and frequently associated with super-enhancers. We conclude that CDK7 mediates transcriptional addiction to a vital cluster of genes in TNBC and CDK7 inhibition may be a useful therapy for this challenging cancer.
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