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

Author

Listed:
  • David P. Labbé

    (Harvard Medical School
    Dana-Farber Cancer Institute
    McGill University and Research Institute of the McGill University Health Centre)

  • Giorgia Zadra

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital)

  • Meng Yang

    (Harvard T.H. Chan School of Public Health)

  • Jaime M. Reyes

    (Harvard Medical School)

  • Charles Y. Lin

    (Baylor College of Medicine)

  • Stefano Cacciatore

    (Cancer Genomics Group, International Centre for Genetic Engineering and Biotechnology)

  • Ericka M. Ebot

    (Harvard T.H. Chan School of Public Health)

  • Amanda L. Creech

    (The Broad Institute of MIT and Harvard University)

  • Francesca Giunchi

    (Pathology Service, Addarii Institute of Oncology, S-Orsola-Malpighi Hospital)

  • Michelangelo Fiorentino

    (Pathology Service, Addarii Institute of Oncology, S-Orsola-Malpighi Hospital)

  • Habiba Elfandy

    (Dana-Farber Cancer Institute)

  • Sudeepa Syamala

    (Dana-Farber Cancer Institute)

  • Edward D. Karoly

    (Metabolon)

  • Mohammed Alshalalfa

    (Decipher Biosciences)

  • Nicholas Erho

    (Decipher Biosciences)

  • Ashley Ross

    (Johns Hopkins Medical Institutions)

  • Edward M. Schaeffer

    (Northwestern University Feinberg School of Medicine)

  • Ewan A. Gibb

    (Decipher Biosciences)

  • Mandeep Takhar

    (Decipher Biosciences)

  • Robert B. Den

    (Sidney Kimmel Medical College at Thomas Jefferson University)

  • Jonathan Lehrer

    (Decipher Biosciences)

  • R. Jeffrey Karnes

    (Mayo Clinic Rochester)

  • Stephen J. Freedland

    (Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center
    Durham Veteran Affairs Medical Center)

  • Elai Davicioni

    (Decipher Biosciences)

  • Daniel E. Spratt

    (University of Michigan)

  • Leigh Ellis

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    The Broad Institute of MIT and Harvard University)

  • Jacob D. Jaffe

    (The Broad Institute of MIT and Harvard University)

  • Anthony V. DʼAmico

    (Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School)

  • Philip W. Kantoff

    (Harvard Medical School
    Memorial Sloan Kettering Cancer Center)

  • James E. Bradner

    (Harvard Medical School)

  • Lorelei A. Mucci

    (Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital, Harvard Medical School)

  • Jorge E. Chavarro

    (Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health
    Brigham and Women’s Hospital, Harvard Medical School)

  • Massimo Loda

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    The Broad Institute of MIT and Harvard University
    New York Presbyterian-Weill Cornell Campus)

  • Myles Brown

    (Harvard Medical School
    Dana-Farber Cancer Institute)

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.

Suggested Citation

  • David P. Labbé & Giorgia Zadra & Meng Yang & Jaime M. Reyes & Charles Y. Lin & Stefano Cacciatore & Ericka M. Ebot & Amanda L. Creech & Francesca Giunchi & Michelangelo Fiorentino & Habiba Elfandy & S, 2019. "High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12298-z
    DOI: 10.1038/s41467-019-12298-z
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    Cited by:

    1. Pallavi Kompella & Guliang Wang & Russell E. Durrett & Yanhao Lai & Celeste Marin & Yuan Liu & Samy L. Habib & John DiGiovanni & Karen M. Vasquez, 2024. "Obesity increases genomic instability at DNA repeat-mediated endogenous mutation hotspots," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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