Document Type
Article
Publication Date
9-25-2019
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.
Recommended Citation
Labbé, David P.; Zadra, Giorgia; Yang, Meng; Reyes, Jaime M; Lin, Charles Y; Cacciatore, Stefano; Ebot, Ericka M.; Creech, Amanda L.; Giunchi, Francesca; Fiorentino, Michelangelo; Elfandy, Habiba; Syamala, Sudeepa; Karoly, Edward D.; Alshalalfa, Mohammed; Erho, Nicholas; Ross, Ashley; Schaeffer, Edward M.; Gibb, Ewan A.; Takhar, Mandeep; Den, Robert B.; Lehrer, Jonathan; Karnes, R. Jeffrey; Freedland, Stephen J.; Davicioni, Elai; Spratt, Daniel E.; Ellis, Leigh; Jaffe, Jacob D.; DʼAmico, Anthony V.; Kantoff, Philip W.; Bradner, James E.; Mucci, Lorelei A.; Chavarro, Jorge E.; Loda, Massimo; and Brown, Myles, "High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program." (2019). Department of Radiation Oncology Faculty Papers. Paper 123.
https://jdc.jefferson.edu/radoncfp/123
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
31554818
Language
English
Comments
This article is the author’s final published version in Nature Communications, Volume 10, Issue 1, September 2019, Page 4358.
The published version is available at https://doi.org/10.1038/s41467-019-12298-z. Copyright © Labbé et al.