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| Status |
Public on Jul 21, 2013 |
| Title |
Tight coordination of protein translation and heat shock factor 1 activation supports the anabolic malignant state [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
A unifying characteristic of aggressive cancers is a profound anabolic shift in metabolism to enable sustained proliferation and biomass expansion. The ribosome is centrally situated to sense metabolic states but whether it impacts systems that promote cellular survival is unknown. Here, through integrated chemical-genetic analyses, we find that a dominant transcriptional effect of blocking protein translation in cancer cells is complete inactivation of heat shock factor 1 (HSF1), a multifaceted transcriptional regulator of the heat-shock response and many other cellular processes essential for tumorigenesis. Translational flux through the ribosome reshapes the transcriptional landscape and links the fundamental anabolic processes of protein production and energy metabolism with HSF1 activity. Targeting this link deprives cancer cells of their energy and chaperone armamentarium thereby rendering the malignant phenotype unsustainable.
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| Overall design |
We used ChIP-Seq to examine affect of rocaglates and cycloheximide on HSF1 genomic occupancy in MCF7 and M0-91 cancer cells.
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| Contributor(s) |
Santagata S, Mendillo ML, Tang Y, Subramanian A, Perley CC, Roche SP, Wong B, Narayan R, Kwon H, Koeva M, Amon A, Golub TR, Porco JA, Whitesell L, Lindquist S |
| Citation(s) |
23869022 |
| Submission date |
Apr 08, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Marc Mendillo |
| Organization name |
Whitehead Institute for Biomedical Research
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| Street address |
9 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (21)
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| This SubSeries is part of SuperSeries: |
| GSE45853 |
Tight coordination of protein translation and heat shock factor 1 activation supports the anabolic malignant state |
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| Relations |
| BioProject |
PRJNA196591 |
| SRA |
SRP020615 |
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