ArticleProceedings of the National Academy of Sciences of the United States of America2025
Comparative transcriptomics reveals a mixed basal, club, and hillock epithelial cell identity in castration-resistant prostate cancer.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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22citing papers in PubMed
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22 citing papers in PubMed.
- ERG Orchestrates a Dedifferentiation-Senescence-Inflammation Triad in Prostate Cancer.Molecular cancer research : MCR · 2026Article
- Targeting the Androgen Receptor and Associated Cofactors in Prostate Cancer: Novel Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- IRE1 activity is prognostic in localised and metastatic prostate cancer and affects epithelial lineage states.EMBO molecular medicine · 2026Article
- ADT and activation of HGF and WNT axes in double-null prostate cancer.Nature reviews. Urology · 2026Review
- Club (Clara) cells in human prostate: A survival guide for conventional histologists/histopathologists.Histology and histopathology · 2026Review
- Prostate Club-like Cells Reveal Context-Dependent Epithelial States in Homeostasis Remodeling and Cancer.Cells · 2026Review
- Mapping prostate cancer pathobiology: A review of genetically engineered mouse models (GEMMs).Gene · 2026Review
- Therapeutic targeting of the eIF4E cap-binding domain reveals control of lineage fate in prostate cancer.The Journal of clinical investigation · 2026Article
- Insights gained from single-cell transcriptomics on the cellular identity and plasticity of prostate epithelial cells.Prostate cancer and prostatic diseases · 2026Review
- Beyond PSMA: theranostic cell surface targets in metastatic prostate cancer.Prostate cancer and prostatic diseases · 2026Review
- 3D genome architecture and epigenetic regulation of lineage identity in advanced prostate cancer.Endocrinology · 2026Review
- A Double-Negative Prostate Cancer Subtype Is Vulnerable to SWI/SNF-Targeting Degrader Molecules.Cancer research · 2026Article
- Deciphering double-negative prostate cancer: from aggressive subtype to novel therapeutic paradigms.Cell communication and signaling : CCS · 2026Review
- CREB5 regulates stem cell-like transcriptional programs to enhance tumor progression in prostate cancer.Oncotarget · 2026Article
- Targeting pre-existing club-like cells in prostate cancer potentiates androgen deprivation therapy.EMBO molecular medicine · 2026Article
- Integrated single-cell and spatial transcriptomic profiling decodes lineage plasticity and immune microenvironment remodeling in prostate cancer progression.Molecular cancer · 2026Article
- CCL chemokines as prognostic and immunotherapeutic markers in prostate cancer: a comprehensive analysis.World journal of surgical oncology · 2026Article
- EZH2 Suppression Diversifies Prostate Cancer Lineage Variant Evolution and Lacks Efficacy in Inhibiting Disease Progression.Cancer research · 2026Article
- Single-cell and spatial omics of metabolic-immune ecosystems in prostate cancer: from androgen signaling to therapy resistance.Frontiers in immunology · 2026Review
- Tumor-associated macrophages and lineage plasticity in prostate cancer: from established myeloid programs to emerging spatial hypotheses.Frontiers in immunology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
30 authors.
Samuel P PitzenMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.ORCID 0000-0001-6556-0461
Amber N RudenickMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.ORCID 0009-0000-2429-1437
Yinjie QiuMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455.ORCID 0000-0002-0584-0688
Weijie ZhangDepartment of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455.ORCID 0000-0002-8978-8310
Sarah A MunroMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455.
Braedan M McCluskeyMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455.
Colleen ForsterDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455.ORCID 0000-0001-5593-882X
Hannah E BergomDivision of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455.
Atef AliDivision of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455.
Ella BoytimDivision of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455.
John T LafinDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390.ORCID 0000-0003-2335-8999
Simon LinderDivision on Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands 1066 CX.
Mazlina IsmailDepartment of Oncology, University College London Cancer Institute, London, United Kingdom WC1E 6BT.
Wout DevliesDepartment of Urology, University Hospitals Leuven, Leuven 3000, Belgium.ORCID 0000-0003-0725-6300
Conner J SessionsDepartment of Urology, University of Washington, Seattle, WA 98195.ORCID 0009-0004-3810-4099
Frank ClaessensDepartment of Cellular and Molecular Medicine, Katholieke Universiteit Leuven, Leuven 3000, Belgium.ORCID 0000-0002-8676-7709
Steven JoniauDepartment of Urology, University Hospitals Leuven, Leuven 3000, Belgium.
Gerhardt AttardDepartment of Oncology, University College London Cancer Institute, London, United Kingdom WC1E 6BT.
Wilbert ZwartDivision on Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands 1066 CX.
Peter S NelsonDivision of Hematology and Oncology, University of Washington, Fred Hutchinson Cancer Center, Seattle WA 98109.
Eva CoreyDepartment of Urology, University of Washington, Seattle, WA 98195.ORCID 0000-0002-9244-3807
Yuzhuo WangDepartment of Urologic Sciences, Faculty of Medicine, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.ORCID 0000-0002-9749-8591
Joshua M LangDepartment of Medicine, University of Wisconsin-Madison, Madison, WI 53792.ORCID 0000-0002-0943-8872
Himisha BeltranDepartment of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115.ORCID 0000-0003-3259-2226
Douglas StrandDepartment of Urology, University of Texas Southwestern Medical Center, Dallas, TX 75390.ORCID 0000-0002-0746-927X
Emmanuel S AntonarakisMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.ORCID 0000-0003-3531-3851
Justin HwangMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.
Paari MuruganDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455.ORCID 0000-0003-4706-213X
R Stephanie HuangMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.ORCID 0000-0002-9862-0368
Scott M DehmMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455.ORCID 0000-0002-7827-5579
Funding
Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Timothy C. Hallstrom · 1998 to 2026
$100.4MTRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1MSteroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0MMEDICAL SCIENTIST TRAINING PROGRAMT32GM008244 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SHIMIZU, YOJI · 1988 to 2024
$13.6MAR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9MMolecular mechanisms underlying lineage plasticity in prostate cancerR37CA241486 · NCI · DANA-FARBER CANCER INST · PI Himisha Beltran · 2020 to 2026
$4.1MMedical Scientist Training ProgramT32GM156735 · NIGMS · UNIVERSITY OF MINNESOTA · PI YOJI SHIMIZU · 2025 to 2026
$2.6MMolecular regulation and expression of Trop-2 in advanced prostate cancer: Identifying optimal therapeutic nichesR01CA276269 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Scott M. Dehm, Joshua Lang · 2023 to 2026
$2.6MDefining 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
$2.0MTargeting Vulnerabilities Exposed by Cancer Treatment-Induced Lineage PlasticityR01CA266452 · NCI · FRED HUTCHINSON CANCER CENTER · PI PETER S NELSON · 2022 to 2026
$2.0MTargeting early events in prostate cancer lineage plasticityR01CA270539 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2023 to 2026
$1.8MHHS | NIH | National Cancer Institute (NCI) R01CA174777HHS | NIH | National Cancer Institute (NCI) R01CA270539HHS | NIH | National Cancer Institute (NCI) R01CA276269NCI NIH HHS P01 CA163227NCI NIH HHS P30 CA077598NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA234715NCI NIH HHS R01 CA266452NCI NIH HHS R01 CA270539NCI NIH HHS R01 CA276269NCI NIH HHS R37 CA241486NIGMS NIH HHS T32 GM008244NIGMS NIH HHS T32 GM156735
Abstract
Inhibiting the androgen receptor (AR) is effective for treatment of advanced prostate cancers because of their AR-dependent luminal epithelial cell identity. Tumors progress during therapy to castration-resistant prostate cancer (CRPC) by restoring AR signaling and maintaining luminal identity or by converting through lineage plasticity to a neuroendocrine (NE) identity or double-negative CRPC (DNPC) lacking luminal or NE identities. Here, we show that DNPC cells express genes defining basal, club, and hillock epithelial cells from benign prostate. We identified KLF5 as a regulator of genes defining this mixed basal, club, and hillock cell identity in DNPC models. KLF5-mediated upregulation of
Indexed as
Epithelial CellsProstatic Neoplasms, Castration-ResistantTranscriptomeCell Line, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKruppel-Like Transcription FactorsMaleProstateReceptors, AndrogenReceptors, Retinoic AcidAR protein, humanKLF5 protein, humanKruppel-Like Transcription FactorsReceptors, AndrogenReceptors, Retinoic Acidcastration-resistant prostate cancercell identityKLF5lineage plasticity
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