ArticleNature genetics2025
Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer.
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Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5citing papers in PubMed
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Who cites it
5 citing papers in PubMed.
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Therapeutic targeting of the eIF4E cap-binding domain reveals control of lineage fate in prostate cancer.The Journal of clinical investigation · 2026Article
- Nuclear prostaglandin E synthase 3 promotes hepatocellular carcinoma growth with immunosuppressive macrophage polarization via the SP1/TGF-β axis.Molecular biomedicine · 2026Article
- Identification of G4-regulated immune-related drug targets for prostate cancer based on G4 screen and machine learning.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
39 authors.
Haolong LiHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. haolongli@fredhutch.org.ORCID http://orcid.org/0000-0002-8628-9698
James E MelnykDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
Becky Xu Hua FuHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Raunak ShresthaHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1144-1413
Meng ZhangHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1042-6294
Martin SjöströmHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2629-9966
Siyu FengThe UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA.
Jasmine A AndersonHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0009-0006-7791-7206
Wanting HanHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-2173-3647
Lisa N ChesnerHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Hyun Jin ShinHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Tatyanah FarshHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0000-8058-1033
Humberto J SuarezDepartment of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Seema NathDepartment of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0002-8362-1165
Jonathan ChouHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1258-0391
Rajdeep DasHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Emily A EgusaHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Marsha CalvertHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Audrey KishishitaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Abhilash BarpandaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Jun ZhuHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Ashutosh MaheshwariHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7107-0933
William S ChenHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Mohammed AlshalalfaDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8405-3035
Aidan WintersArc Institute, Palo Alto, CA, USA.
Junjie T HuaHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Tianyi LiuHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Elai DavicioniVeracyte Inc, San Diego, CA, USA.
Arun P WiitaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7465-6964
Bradley A StohrHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Javed SiddiquiDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Bo HuangDepartment of Pharmaceutical Chemistry, University of CaliforniaSan Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1704-4141
Eric J SmallHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3191-6268
Kevan M ShokatDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA.
Peter S NelsonHuman Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5451-5726
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4726-1473
Elizabeth V WasmuthDepartment of Biochemistry and Structural Biology, Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Luke A GilbertHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA. luke@arcinstitute.org.ORCID http://orcid.org/0000-0001-5854-0825
Felix Y FengHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0963-7687
Funding
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4MTRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6MUCSF Specialized Programs of Research Excellence (SPOREs) in Prostate CancerP50CA275741 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ERIC J SMALL · 2024 to 2026
$8.8MBio-Organic Biomedical Mass Spectromy ResourceP41GM103481 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BURLINGAME, ALMA L · 2012 to 2015
$6.4MImproving the efficacy of mTOR inhibitionR01CA221969 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FAN, QI WEN, SHOKAT, KEVAN M. · 2018 to 2022
$2.9MMolecular Mechanisms of Castration Resistant Prostate Cancer Recurrence & Therapeutic StrategiesR01CA227025 · NCI · WASHINGTON UNIVERSITY · PI FENG, FELIX YI-CHUNG, MAHAJAN, NUPAM P · 2019 to 2023
$2.8MDNA repair alterations in metastatic prostate cancer: functional and therapeutic implicationsR01CA230516 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHWORTH, ALAN, FENG, FELIX YI-CHUNG · 2018 to 2022
$2.7MStructural surfaceomics to probe conformation-selective immunotherapy targetsR01CA290875 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Lan Huang, Arun P. Wiita · 2024 to 2026
$2.7MMapping endogenous protein dynamics in living cellsR01GM131641 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Bo Huang · 2019 to 2026
$2.6MA GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4MDefining 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
$2.0MNCI NIH HHS DP2 CA239597NCI NIH HHS F32 CA236347NCI NIH HHS K99 CA204602NCI NIH HHS P30 CA015704NCI NIH HHS P50 CA097186NCI NIH HHS P50 CA186786NCI NIH HHS P50 CA275741NCI NIH HHS R00 CA204602NCI NIH HHS R01 CA221969NCI NIH HHS R01 CA227025NCI NIH HHS R01 CA230516NCI NIH HHS R01 CA234715NCI NIH HHS R01 CA244550NCI NIH HHS R01 CA266452NCI NIH HHS R01 CA290875NIGMS NIH HHS P41 GM103481NIGMS NIH HHS R00 GM140264NIGMS NIH HHS R01 GM124334NIGMS NIH HHS R01 GM131641NIH HHS S10 OD016229Prostate Cancer Foundation (PCF) 17CHAL06Prostate Cancer Foundation (PCF) 21YOUN12Prostate Cancer Foundation (PCF) PC230420Prostate Cancer Foundation (PCF) YIProstate Cancer Foundation (PCF) young investigatorProstate Cancer Foundation (PCF) Young Investigator AwardUC | UC San Francisco | Department of Medicine, University of California, San Francisco (UCSF Department of Medicine) Prostate Cancer Program 2021 Pilot Research AwardsU.S. Department of Defense (United States Department of Defense) HT9425-23-1-0462U.S. Department of Defense (United States Department of Defense) W81XWH-20-1-0136U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1F32CA236347-01U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA221969-01U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA227025U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA230516-01U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1R01CA244550U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA204602U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA230516-02S1U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P50CA097186 PNW Prostate Cancer SPORE Career Enhancement ProgramU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P50CA186786U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM124334U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) R01GM131641Vetenskapsrådet (Swedish Research Council) 2018-00382V Foundation for Cancer Research (V Foundation) V2024-016
Abstract
The androgen receptor (AR) is a critical driver of prostate cancer (PCa). Here, to study regulators of AR protein levels and oncogenic activity, we developed a live-cell quantitative endogenous AR fluorescent reporter. Leveraging this AR reporter, we performed genome-scale CRISPRi flow cytometry sorting screens to systematically identify genes that modulate AR protein levels. We identified and validated known AR protein regulators, including HOXB13 and GATA2, and also unexpected top hits including PTGES3-a poorly characterized gene in PCa. PTGES3 repression resulted in loss of AR protein, cell-cycle arrest and cell death in AR-driven PCa models. Clinically, analysis of PCa data demonstrates that PTGES3 expression is associated with AR-directed therapy resistance. Mechanistically, we show PTGES3 binds directly to AR, regulates AR protein stability and is necessary for AR function in the nucleus at AR target genes. PTGES3 represents a potential therapeutic target for overcoming known mechanisms of resistance to existing AR-directed therapies in PCa.
Indexed as
Prostatic NeoplasmsReceptors, AndrogenCell Line, TumorCRISPR-Cas SystemsDrug Resistance, NeoplasmGATA2 Transcription FactorGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansMaleAR protein, humanGATA2 protein, humanGATA2 Transcription FactorHomeodomain ProteinsHOXB13 protein, humanReceptors, Androgen
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