ArticleOncotarget2016
Lysine demethylase 2A promotes stemness and angiogenesis of breast cancer by upregulating Jagged1.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Structure and mechanism of inhibition of lysine demethylase 2A (KDM2A) by compound 183c.Communications chemistry · 2026Article
- Transcriptomic Signature and PROTAC Strategy Revealed Histone Lysine Demethylase as a Target of Anticancer Activity of Deferiprone.ACS omega · 2026Article
- Posttranslational modifications in regulating Notch signaling pathway and tumor angiogenesis: from molecular mechanisms to therapeutic applications.Journal of molecular cell biology · 2026Review
- Transcriptomic Signature and PROTAC Strategy Revealed Histone Lysine Demethylase as a Target of Anticancer Activity of Deferiprone.bioRxiv : the preprint server for biology · 2025Article
- Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.Medical oncology (Northwood, London, England) · 2025Review
- Effects and mechanisms of exosomes in microenvironment angiogenesis in breast cancer: An updated review.Oncology research · 2025Review
- An RNA damage response network mediates the lethality of 5-FU in colorectal cancer.Cell reports. Medicine · 2024Article
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- A novel STAT3/ NFκB p50 axis regulates stromal-KDM2A to promote M2 macrophage-mediated chemoresistance in breast cancer.Cancer cell international · 2023Article
- Review
- An RNA Damage Response Network Mediates the Lethality of 5-FU in Clinically Relevant Tumor Types.bioRxiv : the preprint server for biology · 2023Article
- CRISPR/Cas9 Screening for Identification of Genes Required for the Growth of Ovarian Clear Cell Carcinoma Cells.Current issues in molecular biology · 2022Article
- Unconventional protein post-translational modifications: the helmsmen in breast cancer.Cell & bioscience · 2022Review
- HOXA-AS2 contributes to regulatory T cell proliferation and immune tolerance in glioma through the miR-302a/KDM2A/JAG1 axis.Cell death & disease · 2022Article
- Co-Targeting Tumor Angiogenesis and Immunosuppressive Tumor Microenvironment: A Perspective in Ethnopharmacology.Frontiers in pharmacology · 2022Review
- Potential epigenetic molecular regulatory networks in ocular neovascularization.Frontiers in genetics · 2022Review
- Nanotechnological Approaches for the Treatment of Triple-Negative Breast Cancer: A Comprehensive Review.Current drug metabolism · 2022Review
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Histone demethylase KDM2A: Biological functions and clinical values (Review).Experimental and therapeutic medicine · 2021Review
- Reciprocal activation of HEY1 and NOTCH4 under SOX2 control promotes EMT in head and neck squamous cell carcinoma.International journal of oncology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alterations of histone methylation dynamically regulated by methyltransferases and demethylases are frequently found in human cancers. Here, we showed that expression of lysine demethylase 2A (KDM2A) is markedly increased in human breast cancer and its overexpression is associated with tumor progression and poor prognosis. Knockdown of KDM2A in breast cancer cells reduced proliferation but not viability. Gene set enrichment analysis revealed that inhibition of KDM2A down-regulates angiogenic genes with concurrent reduction of Jagged1 (JAG1), NOTCH1 and HEY1 in the NOTCH signaling. Chromatin immunoprecipitation- quantitative polymerase chain reaction (ChIP-qPCR) demonstrated the binding of KDM2A to the JAG1 promoter and the increase of methylation of Lys-36 of histone H3 (H3K36) in KDM2A-depleted MDA-MB-231 cells. Tumorsphere formation was significantly reduced in KDM2A-depleted cells which could be reversed by ectopic expression of JAG1. A selective KDM2A inhibitor daminozide also decreased the number of tumorsphere and the number of CD24-/CD44hi cells. In addition, daminozide acted synergistically with cisplatin in cell killing. We identified SOX2 as a direct transcriptional target of KDM2A to promote cancer stemness. Depletion of KDM2A in MDA-MB-231 cells attenuated NOTCH activation and tube formation in co-cultured endothelial cells. Two pro-angiogenic factors JAG1 and PDGFA are key mediators for KDM2A to enhance angiogenesis. Finally, inhibition of KDM2A significantly decreased tumor growth and angiogenesis in orthotopic animal experiments. Collectively, we conclude that KDM2A functions as an oncogene in breast cancer by upregulating JAG1 to promote stemness, chemoresistance and angiogenesis.
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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.