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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 25, 2019
- Source ID
- 10.1038/s41467-019-12298-z
Entities
People
- Amanda L. Creech
- Anthony V. Dʼamico
- Ashley J. Ross
- Charles Y Lin
- Daniel E. Spratt
- David Labbé
- Edward D. Karoly
- Edward M. Schaeffer
- Elai Davicioni
- Ericka M Ebot
- Ewan A. Gibb
- Francesca Giunchi
- Giorgia Zadra
- Habiba Elfandy
- Jacob D Jaffe
- Jaime M Reyes
- James E. Bradner
- Jonathan Lehrer
- Jorge E. Chavarro
- Leigh Ellis
- Lorelei A. Mucci
- Mandeep Takhar
- Massimo Loda
- Meng Yang
- Michelangelo Fiorentino
- Mohammed Alshalalfa
- Myles A. Brown
- Nicholas Erho
- Philip W. Kantoff
- R. Jeffrey Karnes
- Robert B. Den
- Stefano Cacciatore
- Stephen J. Freedland
- Sudeepa Syamala
Organizations
- Cancer Research Society
- Dana–Farber Cancer Institute
- Istituto Superiore di Sanità
- Prostate Cancer Foundation
- United States Department of Defense