Evidence map›Paper›PMID 38932701›Full record

ArticleNucleic acids research2024

ONECUT2 acts as a lineage plasticity driver in adenocarcinoma as well as neuroendocrine variants of prostate cancer.

Chen Qian, Qian Yang, Mirja Rotinen, Rongrong Huang, Hyoyoung Kim, Brad Gallent, Yiwu Yan, Radu M Cadaneanu, Baohui Zhang, Salma Kaochar and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
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

32 citing papers in PubMed.

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  19. Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026
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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

26 authors.

Chen QianDepartments of Urology and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.ORCID 0000-0002-9803-5740
Qian YangDepartments of Urology and Computational Biomedicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Mirja RotinenDepartment of Health Sciences, Public University of Navarre, Pamplona, Navarra, Spain.
Rongrong HuangDepartment of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA 90095, USA.
Hyoyoung KimDepartments of Urology and Computational Biomedicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Brad GallentDepartments of Urology and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Yiwu YanDepartments of Urology and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Radu M CadaneanuDepartment of Surgical and Perioperative Care, VA Greater Los Angeles; Department of Urology and Jonsson Comprehensive Cancer Center, the David Geffen School of Medicine, UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA 90095, USA.
Baohui ZhangDepartment of Surgical and Perioperative Care, VA Greater Los Angeles; Department of Urology and Jonsson Comprehensive Cancer Center, the David Geffen School of Medicine, UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA 90095, USA.
Salma KaocharDepartment of Medicine Section Hematology/Oncology Baylor College of Medicine, Houston, 77030 TX, USA.
Stephen J FreedlandDepartments of Urology and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Edwin M PosadasDivision of Medical Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Leigh EllisCenter for Prostate Disease Research, Mutha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20814, USA.
Dolores Di VizioDepartments of Urology, Pathology and Laboratory Medicine, and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Colm MorrisseyDepartment of Urology, University of Washington, Seattle, WA 98195, USA.
Peter S NelsonDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Lauren BradyDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Ramachandran MuraliDepartments of Urology and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Moray J CampbellSamuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.ORCID 0000-0002-3355-0928
Wei YangDepartment of Pathology and Cancer Center, Stony Brook University, NY 11794, USA.
Beatrice S KnudsenHuntsman Cancer Institute, University of Utah, Salt Lake City, UT 84108, USA.
Elahe A MostaghelGeriatric Research, Education and Clinical Center (GRECC), U.S. Department of Veterans Affairs Puget Sound Health Care System, Seattle, WA 98133, USA.
Huihui YeDepartment of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Isla P GarrawayDepartment of Surgical and Perioperative Care, VA Greater Los Angeles; Department of Urology and Jonsson Comprehensive Cancer Center, the David Geffen School of Medicine, UCLA, Box 951738, 10833 Le Conte Ave 66-188 CHS UCLA, Los Angeles, CA 90095, USA.
Sungyong YouDepartments of Urology and Computational Biomedicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Michael R FreemanDepartments of Urology and Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REITER, ROBERT E · 2002 to 2023
$42.6M
Racial Differences in Prostate Cancer Molecular SubtypingR01CA220327 · NCI · CEDARS-SINAI MEDICAL CENTER · PI Stephen Jay Freedland, Michael R. Freeman · 2018 to 2026
$3.1M
Mechanisms of Prostate Cancer MetastasisR01CA271750 · NCI · CEDARS-SINAI MEDICAL CENTER · PI FREEMAN, MICHAEL R., GARRAWAY, ISLA PEARL · 2021 to 2025
$2.2M
Defining and Targeting Lineage Transition Programs Operative in AR Pathway Independent Prostate CancerR01CA234715 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NELSON, PETER S · 2020 to 2024
$2.0M
Targeting Vulnerabilities Exposed by Cancer Treatment-Induced Lineage PlasticityR01CA266452 · NCI · FRED HUTCHINSON CANCER CENTER · PI PETER S NELSON · 2022 to 2026
$2.0M
A multidisciplinary training program in prostate cancerT32CA240172 · NCI · CEDARS-SINAI MEDICAL CENTER · PI BHOWMICK, NEIL A., FREEDLAND, STEPHEN JAY · 2019 to 2023
$988k
A Prostate Cancer Dependency Map to Identify Tumor Subtype-Specific VulnerabilitiesR21CA277368 · NCI · FRED HUTCHINSON CANCER CENTER · PI NELSON, PETER S · 2023 to 2024
$442k
Department of Defense PC180541Institute for Prostate Cancer Research P50CA97186NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA092131NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA220327NCI NIH HHS R01 CA234715NCI NIH HHS R01 CA266452NCI NIH HHS R01 CA271750NCI NIH HHS R21 CA277368NCI NIH HHS T32 CA240172UCLA Prostate Cancer SPORE 2P50CA092131
6 · The paper itself

Abstract

Androgen receptor- (AR-) indifference is a mechanism of resistance to hormonal therapy in prostate cancer (PC). Here we demonstrate that ONECUT2 (OC2) activates resistance through multiple drivers associated with adenocarcinoma, stem-like and neuroendocrine (NE) variants. Direct OC2 gene targets include the glucocorticoid receptor (GR; NR3C1) and the NE splicing factor SRRM4, which are key drivers of lineage plasticity. Thus, OC2, despite its previously described NEPC driver function, can indirectly activate a portion of the AR cistrome through epigenetic activation of GR. Mechanisms by which OC2 regulates gene expression include promoter binding, enhancement of genome-wide chromatin accessibility, and super-enhancer reprogramming. Pharmacologic inhibition of OC2 suppresses lineage plasticity reprogramming induced by the AR signaling inhibitor enzalutamide. These results demonstrate that OC2 activation promotes a range of drug resistance mechanisms associated with treatment-emergent lineage variation in PC and support enhanced efforts to therapeutically target OC2 as a means of suppressing treatment-resistant disease.

Indexed as

AdenocarcinomaBenzamidesDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticNitrilesProstatic NeoplasmsReceptors, AndrogenReceptors, GlucocorticoidAnimalsCell LineageCell Line, TumorEpigenesis, GeneticHumansMaleMiceNerve Tissue ProteinsAR protein, humanBenzamidesenzalutamideNerve Tissue ProteinsNitrilesNR3C1 protein, humanPhenylthiohydantoinReceptors, AndrogenReceptors, GlucocorticoidRNA-Binding ProteinsSRRM4 protein, human

Identifiers

PMID38932701
PMCPMC11260453

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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.