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| Status |
Public on Aug 07, 2012 |
| Title |
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers [gene expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their non-transformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, even these genes are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.
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| Overall design |
We used microarrays to examine affect of HSF1 depletion on gene expression in cancer cell lines. Three cancer cell lines (BPLER, HMLER & MCF7) were transduced with either control shRNAi (Scramble or GFP) or an shRNAi that targets and depletes HSF1 (hA6). Another BPLER sample was subjected to a 1H, 42˚ C heat shock. Two biological replicates for all samples.
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| Contributor(s) |
Mendillo ML, Santagata S, Koeva M, Bell GW, Hu R, Tamimi RM, Fraenkel E, Ince TI, Whitesell L, Lindquist S |
| Citation(s) |
22863008 |
| Submission date |
May 24, 2012 |
| Last update date |
Jan 17, 2017 |
| Contact name |
Marc Mendillo |
| Organization name |
Whitehead Institute for Biomedical Research
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| Street address |
9 Cambridge Center
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL3921 |
[HT_HG-U133A] Affymetrix HT Human Genome U133A Array |
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| Samples (20)
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| This SubSeries is part of SuperSeries: |
| GSE38912 |
HSF1 drives a transcriptional program distinct from heat shock to support highly malignant human cancers |
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| Relations |
| BioProject |
PRJNA167461 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38232_RAW.tar |
45.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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