ArticleCancer research2020
Inhibition of Histone H3K27 Demethylases Inactivates Brachyury (TBXT) and Promotes Chordoma Cell Death.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 61 citations in OpenAlex.
- The copy-number events in skull base chordoma stratify tumours into four biologically coherent groups.Neoplasia (New York, N.Y.) · 2026Article
- Review
- Targeting chordoma via an isocitrate dehydrogenase-1-dependent susceptibility to redox metabolism.Acta neuropathologica · 2026Article
- ID3 deficiency alters chromatin accessibility at DSB sites and enhances vulnerability to HDAC inhibition.International journal of cancer · 2026Article
- Immune infiltration is associated with distinct transcriptional states and metabolic profiles in chordomas.iScience · 2026Article
- ATF4-mediated stress response as a therapeutic vulnerability in chordoma.Molecular oncology · 2026Article
- KDM6B inhibition enhances chemotherapeutic response in small cell lung cancer via epigenetic regulation of apoptosis and ferroptosis.Cell & bioscience · 2025Article
- The TBXT rs2305089 SNP links the benign notochordal cell tumour and chordoma.The Journal of pathology · 2025Article
- Chromatin Interaction and Histone Mark Signatures Associated With TBXT Expression in Metastatic Lung Cancer.Genes, chromosomes & cancer · 2025Article
- Mutation on JmjC domain of UTX impaired its antitumor effects in pancreatic cancer via inhibiting G0S2 expression and activating the Toll-like signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Three-dimensional virtual reality-assisted surgical planning for neuronavigated sacrectomy of a chordoma: a technical note.International orthopaedics · 2024Article
- Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury.Angewandte Chemie (International ed. in English) · 2024Article
- N6-methyladenosine-modified circTEAD1 stabilizes Yap1 mRNA to promote chordoma tumorigenesis.Clinical and translational medicine · 2024Article
- Airway epithelial cGAS inhibits LPS-induced acute lung injury through CREB signaling.Cell death & disease · 2023Article
- Predicting overall survival in chordoma patients using machine learning models: a web-app application.Journal of orthopaedic surgery and research · 2023Article
- DNA methylation, combined with RNA sequencing, provide novel insight into molecular classification of chordomas and their microenvironment.Acta neuropathologica communications · 2023Article
- Plasma cell-free DNA methylome profiling in pre- and post-surgery oral cavity squamous cell carcinoma.Molecular carcinogenesis · 2023Article
- The malignancy of chordomas is enhanced via a circTLK1/miR-16-5p/Smad3 positive feedback axis.Cell death discovery · 2023Article
- Phenotypic Chemical Screening in CD4Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Expression of the transcription factor brachyury (TBXT) is normally restricted to the embryo, and its silencing is epigenetically regulated. TBXT promotes mesenchymal transition in a subset of common carcinomas, and in chordoma, a rare cancer showing notochordal differentiation, TBXT acts as a putative oncogene. We hypothesized that TBXT expression is controlled through epigenetic inhibition to promote chordoma cell death. Screening of five human chordoma cell lines revealed that pharmacologic inhibition of the histone 3 lysine 27 demethylases KDM6A (UTX) and KDM6B (JMJD3) leads to cell death. This effect was phenocopied by dual genetic inactivation of KDM6A/B using CRISPR/Cas9. Inhibition of KDM6A/B with a novel compound KDOBA67 led to a genome-wide increase in repressive H3K27me3 marks with concomitant reduction in active H3K27ac, H3K9ac, and H3K4me3 marks.
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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.