Evidence map›Paper›PMID 36181613›Full record

ArticleDiscover oncology2022

Progression of prostate cancer reprograms MYC-mediated lipid metabolism via lysine methyltransferase 2A.

Nichelle C Whitlock, Margaret E White, Brian J Capaldo, Anson T Ku, Supreet Agarwal, Lei Fang, Scott Wilkinson, Shana Y Trostel, Zhen-Dan Shi, Falguni Basuli and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Discover oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Molecular therapy. Oncology · 2025
    Article
  4. Fueling the fire-a pan-cancer analysis of MYC-regulated lipid metabolism.Frontiers in cell and developmental biology · 2025
    Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 2 institutions in 1 country.

Nichelle C Whitlock *Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Margaret E White *Laboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Brian J CapaldoLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Anson T KuLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Supreet AgarwalLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Lei FangLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Scott WilkinsonLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Shana Y TrostelLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Zhen-Dan ShiChemistry and Synthesis Center, National Heart, Lung and Blood Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Falguni BasuliChemistry and Synthesis Center, National Heart, Lung and Blood Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Karen WongMolecular Imaging Branch, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Elaine M JagodaMolecular Imaging Branch, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Kathleen KellyLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA.
Peter L ChoykeMolecular Imaging Branch, National Cancer Institute, NIH, 10 Center Drive, Bethesda, MD, 20892, USA.
Adam G SowalskyLaboratory of Genitourinary Cancer Pathogenesis, National Cancer Institute, NIH, 37 Convent Drive, Bethesda, MD, 20892, USA. adam.sowalsky@nih.gov.
National Cancer Institute · USNational Heart Lung and Blood Institute · US

Funding

Congressionally Directed Medical Research Programs W81XWH-16-1-0433Congressionally Directed Medical Research Programs W81XWH-19-1-0712NIH HHS Intramural Research Program, National Cancer InstituteNIH HHS Intramural Research Program, National Heart Lung and Blood InstituteProstate Cancer Foundation Young Investigator Award
6 · The paper itself

Abstract

backgroundThe activities of MYC, the androgen receptor, and its associated pioneer factors demonstrate substantial reprogramming between early and advanced prostate cancer. Although previous studies have shown a shift in cellular metabolic requirements associated with prostate cancer progression, the epigenetic regulation of these processes is incompletely described. Here, we have integrated chromatin immunoprecipitation sequencing (ChIP-seq) and whole-transcriptome sequencing to identify novel regulators of metabolism in advanced prostate tumors characterized by elevated MYC activity.

resultsUsing ChIP-seq against MYC, HOXB13, and AR in LNCaP cells, we observed redistribution of co-bound sites suggestive of differential KMT2A activity as a function of MYC expression. In a cohort of 177 laser-capture microdissected foci of prostate tumors, KMT2A expression was positively correlated with MYC activity, AR activity, and HOXB13 expression, but decreased with tumor grade severity. However, KMT2A expression was negatively correlated with these factors in 25 LuCaP patient-derived xenograft models of advanced prostate cancer and 99 laser-capture microdissected foci of metastatic castration-resistant prostate cancer. Stratified by KMT2A expression, ChIP-seq against AR and HOXB13 in 15 LuCaP patient-derived xenografts showed an inverse association with sites involving genes implicated in lipid metabolism, including the arachidonic acid metabolic enzyme PLA2G4F. LuCaP patient-derived xenograft models grown as organoids recapitulated the inverse association between KMT2A expression and fluorine-18 labeled arachidonic acid uptake in vitro.

conclusionsOur study demonstrates that the epigenetic activity of transcription factor oncogenes exhibits a shift during prostate cancer progression with distinctive phenotypic effects on metabolism. These epigenetically driven changes in lipid metabolism may serve as novel targets for the development of novel imaging agents and therapeutics.

Indexed as

Lipid metabolismProstate cancerTranscriptional regulation

Identifiers

PMID36181613
PMCPMC9526773
OpenAlexW4298327028

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.