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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
25 09 2019
Historique:
received: 06 09 2018
accepted: 23 08 2019
entrez: 27 9 2019
pubmed: 27 9 2019
medline: 14 1 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31554818
doi: 10.1038/s41467-019-12298-z
pii: 10.1038/s41467-019-12298-z
pmc: PMC6761092
doi:

Substances chimiques

Proto-Oncogene Proteins c-myc 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

4358

Subventions

Organisme : NCI NIH HHS
ID : R01 CA215452
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA090381
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA187918
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA090598
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL034595
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA155626
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA058684
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA167552
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA040360
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK046200
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA131945
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA042182
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL026490
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA097193
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA163227
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA034944
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA141298
Pays : United States

Commentaires et corrections

Type : CommentIn

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Auteurs

David P Labbé (DP)

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Division of Urology, Department of Surgery, McGill University and Research Institute of the McGill University Health Centre, Montréal, QC, Canada.

Giorgia Zadra (G)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Meng Yang (M)

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Jaime M Reyes (JM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Charles Y Lin (CY)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Stefano Cacciatore (S)

Cancer Genomics Group, International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa.

Ericka M Ebot (EM)

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Amanda L Creech (AL)

The Broad Institute of MIT and Harvard University, Cambridge, MA, USA.

Francesca Giunchi (F)

Pathology Service, Addarii Institute of Oncology, S-Orsola-Malpighi Hospital, Bologna, IT, Italy.

Michelangelo Fiorentino (M)

Pathology Service, Addarii Institute of Oncology, S-Orsola-Malpighi Hospital, Bologna, IT, Italy.

Habiba Elfandy (H)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.

Sudeepa Syamala (S)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.

Edward D Karoly (ED)

Metabolon, Morrisville, NC, USA.

Mohammed Alshalalfa (M)

Decipher Biosciences, Vancouver, BC, Canada.

Nicholas Erho (N)

Decipher Biosciences, Vancouver, BC, Canada.

Ashley Ross (A)

James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Edward M Schaeffer (EM)

Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Ewan A Gibb (EA)

Decipher Biosciences, Vancouver, BC, Canada.

Mandeep Takhar (M)

Decipher Biosciences, Vancouver, BC, Canada.

Robert B Den (RB)

Department of Radiation Oncology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA.

Jonathan Lehrer (J)

Decipher Biosciences, Vancouver, BC, Canada.

R Jeffrey Karnes (RJ)

Department of Urology, Mayo Clinic Rochester, Rochester, MN, USA.

Stephen J Freedland (SJ)

Department of Surgery, Division of Urology, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Surgery Section, Durham Veteran Affairs Medical Center, Durham, NC, USA.

Elai Davicioni (E)

Decipher Biosciences, Vancouver, BC, Canada.

Daniel E Spratt (DE)

Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.

Leigh Ellis (L)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
The Broad Institute of MIT and Harvard University, Cambridge, MA, USA.

Jacob D Jaffe (JD)

The Broad Institute of MIT and Harvard University, Cambridge, MA, USA.

Anthony V DʼAmico (AV)

Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Philip W Kantoff (PW)

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

James E Bradner (JE)

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Lorelei A Mucci (LA)

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Jorge E Chavarro (JE)

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Massimo Loda (M)

Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. mloda@med.cornell.edu.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. mloda@med.cornell.edu.
The Broad Institute of MIT and Harvard University, Cambridge, MA, USA. mloda@med.cornell.edu.
Department of Pathology and Laboratory Medicine, Weil Cornell Medicine, New York Presbyterian-Weill Cornell Campus, New York, NY, USA. mloda@med.cornell.edu.

Myles Brown (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. myles_brown@dfci.harvard.edu.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA. myles_brown@dfci.harvard.edu.

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