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Series GSE90905 Query DataSets for GSE90905
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 Expression 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.
Overall design RNA-Seq for 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
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 (15)
GSM2417316 CTD_WT_1
GSM2417317 CTD_WT_2
GSM2417318 CTD_WT_3
This SubSeries is part of SuperSeries:
GSE90912 High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program
BioProject PRJNA356304
SRA SRP094583

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE90905_labbe_diet_switch_fpkm.txt.gz 1.0 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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