Metabolomics

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High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program


ABSTRACT: 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. 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 increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.

INSTRUMENT(S): Q Exactive

SUBMITTER: Massimo Loda 

PROVIDER: MTBLS135 | MetaboLights | 2019-08-22

REPOSITORIES: MetaboLights

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High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program.

Labbé David P DP   Zadra Giorgia G   Yang Meng M   Reyes Jaime M JM   Lin Charles Y CY   Cacciatore Stefano S   Ebot Ericka M EM   Creech Amanda L AL   Giunchi Francesca F   Fiorentino Michelangelo M   Elfandy Habiba H   Syamala Sudeepa S   Karoly Edward D ED   Alshalalfa Mohammed M   Erho Nicholas N   Ross Ashley A   Schaeffer Edward M EM   Gibb Ewan A EA   Takhar Mandeep M   Den Robert B RB   Lehrer Jonathan J   Karnes R Jeffrey RJ   Freedland Stephen J SJ   Davicioni Elai E   Spratt Daniel E DE   Ellis Leigh L   Jaffe Jacob D JD   DʼAmico Anthony V AV   Kantoff Philip W PW   Bradner James E JE   Mucci Lorelei A LA   Chavarro Jorge E JE   Loda Massimo M   Brown Myles M  

Nature communications 20190925 1


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. 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  ...[more]

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