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

Nature Communications, ISSN: 2041-1723, Vol: 10, Issue: 1, Page: 4358
2019
  • 109
    Citations
  • 0
    Usage
  • 174
    Captures
  • 4
    Mentions
  • 206
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    109
  • Captures
    174
  • Mentions
    4
    • News Mentions
      4
      • News
        4
  • Social Media
    206
    • Shares, Likes & Comments
      206
      • Facebook
        206

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Article Description

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.

Bibliographic Details

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; Brown, Myles

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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