ArticleCancer cell2018
KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance.
Erratum issuedOpen access · bronzeAbstract read
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Article in Cancer cell, 2018. 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 157 papers.
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157citing papers in PubMed
10.2field-weighted citation impact, top 1% of its field
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Who cites it
157 citing papers in PubMed, 249 citations in OpenAlex.
- Clonal lineage tracing and parallel multiomics profiling reveal transcriptional heterogeneity induced by ARID1A deficiency.Science advances · 2026Article
- Nuclear SOX9 Expression and Short-Term Survival Outcomes in Early-Stage Luminal Breast Cancer: An Immunohistochemical and Retrospective Cohort Analysis.International journal of molecular sciences · 2026Article
- Targeting galactose metabolic reprogramming overcomes immunotherapy resistance in KRAS-mutant lung adenocarcinoma: Integrative multi-omics and machine learning approaches.Translational oncology · 2026Article
- miR-770-5p regulates KDM5B and links its nuclear localization to HER2 signaling in trastuzumab-resistant breast cancer.Molecular and cellular biochemistry · 2026Article
- JARID1B-Mediated H3K4me3 Demethylation Promotes Cisplatin Resistance in Oral Squamous Cell Carcinoma Cells via the miR-495-3p/FUBP1 Axis.Applied biochemistry and biotechnology · 2026Article
- Inhibition of KDM5A/B promotes antitumor innate immune responses in HHV-8/KSHV-positive B-cell lymphomas.Npj viruses · 2026Article
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Review
- Co-occurrence of transcriptionally distinct persister cell states underpins neoadjuvant therapy resistance in triple‑negative breast cancer.Genome medicine · 2026Article
- Evolutionary dynamics under phenotypic uncertainty.bioRxiv : the preprint server for biology · 2026Article
- Ubiquitin-mediated stabilization of KDM5B drives chemoresistance via repression of dual-specificity phosphatase 4 in ovarian cancer.Signal transduction and targeted therapy · 2026Article
- KDM5B cooperates with CRL4B complex to promote the tumorigenesis of ER+ breast cancer via regulating cholesterol metabolism.Cell death & disease · 2026Article
- Inhibition of KDM5A/B promotes antitumor innate immune responses in HHV-8/KSHV-positive B-cell lymphomas.bioRxiv : the preprint server for biology · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- Human stem cell models for group 3 medulloblastoma uncover JARID1B as a regulator of the chromatin landscape.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- Characterization of Drug-Tolerant Persister Cells in Triple-Negative Breast Cancer Identifies a Shared Persistence Program across Treatments and Patients.Cancer research · 2025Article
- Epigenetic alterations facilitate transcriptional and translational programs in hypoxia.Nature cell biology · 2025Article
- Cold atmospheric plasma restores fulvestrant sensitivity by inhibiting CCND3 in the drug-resistant breast cancer cells.Scientific reports · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
97 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
28 authors at 4 institutions in 1 country.
Kunihiko HinoharaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Hua-Jun WuDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Sébastien VigneauDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Thomas O McDonaldDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kyomi J IgarashiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Kimiyo N YamamotoDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Thomas MadsenDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Anne FasslDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Shawn B EgriThe Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Malvina PapanastasiouThe Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Lina DingDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Guillermo PeluffoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Ofir CohenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Stephen C KalesNational Center for Advancing Translational Sciences, Bethesda, MD 20892, USA.
Madhu Lal-NagNational Center for Advancing Translational Sciences, Bethesda, MD 20892, USA.
Ganesha RaiNational Center for Advancing Translational Sciences, Bethesda, MD 20892, USA.
David J MaloneyNational Center for Advancing Translational Sciences, Bethesda, MD 20892, USA.
Ajit JadhavNational Center for Advancing Translational Sciences, Bethesda, MD 20892, USA.
Anton SimeonovNational Center for Advancing Translational Sciences, Bethesda, MD 20892, USA.
Nikhil WagleDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; The Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Myles BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Ludwig Center at Harvard, Boston, MA 02215, USA.
Alexander MeissnerDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; The Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Piotr SicinskiDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Jacob D JaffeThe Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA.
Rinath JeselsohnDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Alexander A GimelbrantDepartment of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Franziska MichorDepartment of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Ludwig Center at Harvard, Boston, MA 02215, USA. Electronic address: michor@jimmy.harvard.edu.
Kornelia PolyakDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Evolution, Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Ludwig Center at Harvard, Boston, MA 02215, USA. Electronic address: kornelia_polyak@dfci.harvard.edu.
Harvard University · USDana-Farber Cancer Institute · USNational Center for Advancing Translational Sciences · USBroad Institute · US
Funding
Use of Organotypic and Mammary Gland Models to Investigate the Outcomes of ClonalP01CA080111 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI DILLON, DEBORAH · 1999 to 2018
$36.0MTargeting intratumor heterogeneity in breast cancerR35CA197623 · NCI · DANA-FARBER CANCER INST · PI KORNELIA POLYAK · 2015 to 2026
$12.4MTraining Grant in Quantitative Sciences for Cancer ResearchT32CA009337 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI QUACKENBUSH, JOHN, TRIPPA, LORENZO · 1986 to 2025
$12.3MProject 3: Single Cell Measures of Intratumor Diversity for Optimal Breast Cancer TherapyU54CA193461 · NCI · DANA-FARBER CANCER INST · PI POLYAK, KORNELIA · 2015 to 2020
$11.2MThere and Back Again: Epigenetic Reinforcement of Cellular Signaling States - OverallU54HG008097 · NHGRI · BROAD INSTITUTE, INC. · PI PAPANASTASIOU, MARTHA MALVINA, SUBRAMANIAN, ARAVIND · 2014 to 2019
$9.3MNovel functions of D-type and E-type cyclins in normal and in cancer cellsR01CA202634 · NCI · DANA-FARBER CANCER INST · PI SICINSKI, PETER · 2016 to 2020
$2.1MNCI NIH HHS P01 CA080111NCI NIH HHS R01 CA202634NCI NIH HHS R35 CA197623NCI NIH HHS U54 CA193461NHGRI NIH HHS U54 HG008097
Abstract
Members of the KDM5 histone H3 lysine 4 demethylase family are associated with therapeutic resistance, including endocrine resistance in breast cancer, but the underlying mechanism is poorly defined. Here we show that genetic deletion of KDM5A/B or inhibition of KDM5 activity increases sensitivity to anti-estrogens by modulating estrogen receptor (ER) signaling and by decreasing cellular transcriptomic heterogeneity. Higher KDM5B expression levels are associated with higher transcriptomic heterogeneity and poor prognosis in ER
Indexed as
Breast NeoplasmsCell Line, TumorDrug Resistance, NeoplasmEstradiolEstrogen Receptor ModulatorsExome SequencingFemaleFulvestrantGenetic HeterogeneityHumansJumonji Domain-Containing Histone DemethylasesMCF-7 CellsNuclear ProteinsRepressor ProteinsRetinoblastoma-Binding Protein 2TranscriptomeEstradiolEstrogen Receptor ModulatorsFulvestrantJumonji Domain-Containing Histone DemethylasesKDM5A protein, humanKDM5B protein, humanNuclear ProteinsRepressor ProteinsRetinoblastoma-Binding Protein 2acquired resistancebarcodingcellular heterogeneityendocrine resistanceepigeneticKDM5Bpre-existing resistancesingle-cell RNA-seqsubclonal fractiontranscriptomic heterogeneity
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