ArticleThe Journal of clinical investigation2018
ATR inhibition controls aggressive prostate tumors deficient in Y-linked histone demethylase KDM5D.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
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.
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Who cites it
52 citing papers in PubMed, 75 citations in OpenAlex.
- Beyond sex determination: the Y chromosome in male cancers.Nature reviews. Cancer · 2026Review
- Enhancer and metabolic rewiring by KMT2C-COMPASS or KMT2D-COMPASS family loss in cancer creates druggable vulnerabilities.Nature reviews. Cancer · 2026Review
- Evaluation of Loss of the Y Chromosome in Peripheral Blood as a Biomarker for Prostate Cancer.The Prostate · 2026Article
- Lysine demethylase 5D promotes CHEK1 inhibitor sensitivity through p38-mediated cyclooxygenase-2 expression in castration-resistant prostate cancer cells.The Journal of pharmacology and experimental therapeutics · 2025Article
- Y-chromosome alteration and its impact on cancer progression and metastasis.Cellular & molecular biology letters · 2025Review
- Roles of KDM5 demethylases in therapeutic resistance of cancers.Epigenetics & chromatin · 2025Review
- Article
- Sex differences in bladder cancer: understanding biological and clinical implications.Biology of sex differences · 2025Review
- The effects of loss of Y chromosome on male health.Nature reviews. Genetics · 2025Review
- DNA methylation patterns contribute to changes of cellular differentiation pathways in leukocytes with LOY from patients with Alzheimer´s disease.Cellular and molecular life sciences : CMLS · 2025Article
- KDM5D histone demethylase mediates p38α inactivation via its enzymatic activity to inhibit cancer progression.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Comparing the roles of sex chromosome-encoded protein homologs in gene regulation.Genes & development · 2024Review
- Sex chromosome-encoded protein homologs: current progress and open questions.Nature structural & molecular biology · 2024Review
- Y Chromosome Loss and Implications for Oncology.Molecular cancer research : MCR · 2024Review
- The emerging roles of histone demethylases in cancers.Cancer metastasis reviews · 2024Review
- Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications.Nature reviews. Cancer · 2024Article
- The KDM5 inhibitor PBIT reduces proliferation of castration-resistant prostate cancer cells via cell cycle arrest and the induction of senescence.Experimental cell research · 2024Article
- Why Y matters? The implication of loss of Y chromosome in blood and cancer.Cancer science · 2024Review
- Copy number loss of KDM5D may be a predictive biomarker for ATR inhibitor treatment in male patients with pulmonary squamous cell carcinoma.The journal of pathology. Clinical research · 2024Article
- Quantifying Y chromosome loss in primary and metastatic prostate cancer by chromosome painting.PloS one · 2024Article
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
Abstract
Epigenetic modifications control cancer development and clonal evolution in various cancer types. Here, we show that loss of the male-specific histone demethylase lysine-specific demethylase 5D (KDM5D) encoded on the Y chromosome epigenetically modifies histone methylation marks and alters gene expression, resulting in aggressive prostate cancer. Fluorescent in situ hybridization demonstrated that segmental or total deletion of the Y chromosome in prostate cancer cells is one of the causes of decreased KDM5D mRNA expression. The result of ChIP-sequencing analysis revealed that KDM5D preferably binds to promoter regions with coenrichment of the motifs of crucial transcription factors that regulate the cell cycle. Loss of KDM5D expression with dysregulated H3K4me3 transcriptional marks was associated with acceleration of the cell cycle and mitotic entry, leading to increased DNA-replication stress. Analysis of multiple clinical data sets reproducibly showed that loss of expression of KDM5D confers a poorer prognosis. Notably, we also found stress-induced DNA damage on the serine/threonine protein kinase ATR with loss of KDM5D. In KDM5D-deficient cells, blocking ATR activity with an ATR inhibitor enhanced DNA damage, which led to subsequent apoptosis. These data start to elucidate the biological characteristics resulting from loss of KDM5D and also provide clues for a potential novel therapeutic approach for this subset of aggressive prostate cancer.
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Registered trials
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.