@article{c4afe6c48381416397d6e0dc7dd141fa,
title = "High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program",
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.",
author = "Labb{\'e}, {David P.} and Giorgia Zadra and Meng Yang and Reyes, {Jaime M.} and Lin, {Charles Y.} and Stefano Cacciatore and Ebot, {Ericka M.} and Creech, {Amanda L.} and Francesca Giunchi and Michelangelo Fiorentino and Habiba Elfandy and Sudeepa Syamala and Karoly, {Edward D.} and Mohammed Alshalalfa and Nicholas Erho and Ashley Ross and Schaeffer, {Edward M.} and Gibb, {Ewan A.} and Mandeep Takhar and Den, {Robert B.} and Jonathan Lehrer and Karnes, {R. Jeffrey} and Freedland, {Stephen J.} and Elai Davicioni and Spratt, {Daniel E.} and Leigh Ellis and Jaffe, {Jacob D.} and DʼAmico, {Anthony V.} and Kantoff, {Philip W.} and Bradner, {James E.} and Mucci, {Lorelei A.} and Chavarro, {Jorge E.} and Massimo Loda and Myles Brown",
note = "Funding Information: Competing interests: C.Y.L. receives sponsored research from and consults for Kronos Bio, is a shareholder and inventor of IP licensed to Syros Pharmaceuticals, is a shareholder of Amgen, and is an equity partner of Cambridge Science Corporation. M.A., N.E., M.T., J.L., E.A.G. and E.D. are employees of Decipher Biosciences. E.D.K. is currently employed of Metabolon. M.B. receives sponsored research support from Novartis. M.B. is a consultant to Aleta Biotherapeutics and H3 Biomedicine and serves on the SAB of Kronos Bio. The remaining authors declare no competing interests. Funding Information: We thank Zach Herbert, Julie Batista, Noriko Uetani, Cornelia Photopoulos, Radha Kalekar, Maura Cotter, Natalia Scaglia, Teresa Bowman, Nadia Boufaeid (technical assistance and/or helpful discussions), and Sonal Jhaveri (critical review of the manuscript). D.P.L. is a Lewis Katz—Young Investigator of the Prostate Cancer Foundation, and is the recipient of a Scholarship for the Next Generation of Scientists from the Cancer Research Society, and is also recipient of a Canadian Institute of Health Research Fellowship. G.Z. is a recipient of the Idea Development Award from the U.S. Department of Defense (DoD; PC150263) and the Barr Award from the Dana-Farber Cancer Institute. C.Y.L. is a CPRIT Scholar in Cancer Research (RR150093), a Pew-Stewart Scholar for Cancer Research (Alexander and Margaret Stewart Trust), and is funded by the NIH and NCI (1R01CA215452-01). E.M.E. is supported by the DoD Prostate Cancer Research Program Postdoctoral Training Award (W81XWH-14-1-0250). L.E., D.E.S. and L.A.M. are Young Investigators of the Prostate Cancer Foundation. Support for HPFS/PHS cohorts was provided by grants from the DoD (W81XWH-11-1-0529) and grants from the National Institute of Health (NIH; CA42182, CA58684, CA90598, CA141298, CA97193, CA34944, CA40360, CA131945, CA167552, P50CA090381, 1U54CA155626-01, P30DK046200, HL26490 and HL34595). We would like to thank the participants and staff of the HPFS/PHS for their valuable contributions as well as the following state cancer registries for their help: A.L.Z., A.Z., A.R., C.A., C.O., C.T., D.E., F.L., G.A., I.D., I. L., I.N., I.A., K.Y., L.A., M.E., M.D., M.A., M.I., N.E., N.H., N.J., N.Y., N.C., N.D., O.H., O.K., O.R., P.A., R.I., S.C., T.N., T.X., V.A., W.A., W.Y. We assume full responsibility for analyses and interpretation of these data. The work reported here was supported by grants from the NIH (R01CA131945, R01CA187918 to M.L. and P50CA090381 to P.W. K., M.L. and M.B.), the NCI (1P01CA163227 to M.B.) and the Prostate Cancer Foundation to M.L. and M.B. Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-12298-z",
language = "English (US)",
volume = "10",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}