期刊
SCIENCE
卷 341, 期 6143, 页码 250-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1238303
关键词
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资金
- Johnson & Johnson's Corporate Office of Science and Technology
- Marble Fund
- NIH [R01 CA175744-01, K08NS064168]
- NIH Common Fund's LINCS program [5U54HG006093]
- American Cancer Society New England Division-SpinOdyssey [PF-09-253-01-DMC]
- Brain Science Foundation
- American Brain Tumor Association
- Beez Foundation
- V Foundation
- Jared Branfman Sunflowers for Life Fund
- [R03 MH086465-01]
- [R03 DA027713-01]
- [R01 GM073855]
The ribosome is centrally situated to sense metabolic states, but whether its activity, in turn, coherently rewires transcriptional responses is unknown. Here, through integrated chemical-genetic analyses, we found that a dominant transcriptional effect of blocking protein translation in cancer cells was inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for anabolic metabolism, cellular proliferation, and tumorigenesis. These analyses linked translational flux to the regulation of HSF1 transcriptional activity and to the modulation of energy metabolism. Targeting this link with translation initiation inhibitors such as rocaglates deprived cancer cells of their energy and chaperone armamentarium and selectively impaired the proliferation of both malignant and premalignant cells with early-stage oncogenic lesions.
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