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Record W2974971672 · doi:10.1038/s41467-019-12298-z

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

2019· article· en· W2974971672 on OpenAlexafffund
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, Sudeepa Syamala, Edward D. Karoly, Mohammed Alshalalfa, Nicholas Erho, Ashley E. Ross, Edward M. Schaeffer, Ewan A. Gibb, Mandeep Takhar, Robert B. Den, Jonathan Lehrer, R. Jeffrey Karnes, Stephen J. Freedland, Elai Davicioni, Daniel E. Spratt, Leigh Ellis, Jacob D. Jaffe, Anthony V. D’Amico, Philip W. Kantoff, James E. Bradner, Lorelei A. Mucci, Jorge E. Chavarro, Massimo Loda, Myles Brown

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer, Lipids, and Metabolism
Canadian institutionsDecipher Biosciences (Canada)McGill University Health Centre
FundersDOD Prostate Cancer Research ProgramCancer Research SocietyCancer Prevention and Research Institute of TexasAlexander and Margaret Stewart TrustDana-Farber Cancer InstituteNational Cancer InstituteNational Institutes of HealthProstate Cancer FoundationNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood InstituteU.S. Department of Defense
KeywordsProstate cancerProstateCancer researchMetabolomeCancerTumor progressionInternal medicineBiologyHistoneEndocrinologyMedicineGeneGeneticsMetabolite

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.316
Teacher spread0.306 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations182
Published2019
Admission routes2
Has abstractyes

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Same venueNature CommunicationsSame topicCancer, Lipids, and MetabolismFrench-language works237,207