|
| Status |
Public on Aug 21, 2019 |
| Title |
High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality but the molecular underpinnings of this association are poorly understood. Furthermore, the mechanisms by which metabolic rewiring alters the prostate cancer epigenome, the effector arm of intra- and extra-cellular signals, is equally nebulous. Here, we demonstrate, in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to a HFD-dependent phenotype characterized by increased cellular proliferation and tumour burden. Importantly, these results are recapitulated in prostate cancer patients, where increased saturated fat intake (SFI), but not monounsaturated or polyunsaturated fat intake, is also associated with an enhanced MYC transcriptional signature. Additionally, the SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, a dietary intervention consisting of switching from a high-fat to control diet, greatly attenuates the MYC transcriptional program. Our findings suggest that in primary prostate cancer, dietary saturated fat intake contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.
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| |
|
| Overall design |
ChIP-Seq for H4K20me1 and PHF8 of WT and MYC mice fed CTD or HFD
|
| |
|
| Contributor(s) |
Labbé DP, Zadra G, Loda M, Brown M |
| Citation(s) |
31554818 |
| |
| Submission date |
Dec 05, 2016 |
| Last update date |
Oct 08, 2019 |
| Contact name |
James Bradner |
| E-mail(s) |
bradner_computation@dfci.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Bradner Lab
|
| Street address |
450 Brookline
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (8)
|
|
| This SubSeries is part of SuperSeries: |
| GSE90912 |
High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program |
|
| Relations |
| BioProject |
PRJNA356313 |
| SRA |
SRP094586 |
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