High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program
Open accessAbstract
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.
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Diets high in saturated fat potentiate the MYC transcriptional program in human and mouse prostate cancer, enhancing cell proliferation.
“Moreover, diets high in saturated fat potentiate the MYC transcriptional program in human and mouse prostate cancer, enhancing cell proliferation (18).”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [18]
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References 84 · Cited by 174
- Authors
- Labbé, D. P., Zadra, G., Yang, M., Reyes, J. M., Lin, C. Y., Cacciatore, S., Ebot, E. M., Creech, A. L., Giunchi, F., Fiorentino, M., Elfandy, H., Syamala, S., Karoly, E. D., Alshalalfa, M., Erho, N., Ross, A., Schaeffer, E. M., Gibb, E. A., Takhar, M., Den, R. B., Lehrer, J., Karnes, R. J., Freedland, S. J., Davicioni, E., Spratt, D. E., Ellis, L., Jaffe, J. D., DʼAmico, A. V., Kantoff, P. W., Bradner, J. E., Mucci, L. A., Chavarro, J. E., Loda, M., & Brown, M.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Baylor College of Medicine (US)
- International Centre for Genetic Engineering and Biotechnology (ZA)
- Broad Institute (US)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Dana-Farber Cancer Institute (US)
- Metabolon (United States) (US)
- Decipher Biosciences (Canada) (CA)
- Johns Hopkins University (US)
- Northwestern University (US)
- Thomas Jefferson University (US)
- Mayo Clinic (US)
- Cedars-Sinai Medical Center (US)
- University of Michigan (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Loda, Massimo
- Brown, Myles
- ORCID
- Labbé, David P.
- Zadra, Giorgia
- 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.
- Den, Robert B.
- Lehrer, Jonathan
- Karnes, R. Jeffrey
- Freedland, Stephen J.
- Davicioni, Elai
- Spratt, Daniel E.
- Ellis, Leigh
- Jaffe, Jacob D.
- Kantoff, Philip W.
- Bradner, James E.
- Mucci, Lorelei A.
- Chavarro, Jorge E.
- Loda, Massimo
- Brown, Myles
- Venue
- Nature Communications
- Published
- 2019-09-25
- Volume
- 10
- Issue
- 1
- Pages
- 4358-4358
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6761092
- OpenAlex
- W2974971672
- Cited by
- 174
- References
- 84
- Citations by year
- 2026: 13 · 2025: 23 · 2024: 30 · 2023: 28 · 2022: 33 · 2021: 29 · 2020: 17
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- The Medicine Forum (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Prostate Cancer Foundation
- Cancer Research Society
- U.S. Department of Defense
- Dana-Farber Cancer Institute
- National Institute of Health; National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- prostate cancer progression, high-fat diet, saturated fat intake, obesity, tumour proliferation, dietary intervention
- MeSH terms
- Aged, Animals, Humans, Male, Mice, Transgenic, Middle Aged, Prostatic Neoplasms, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myc, Disease Progression, Cell Line, Tumor, Tumor Burden, Cell Proliferation, Metabolome, Diet, High-Fat
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