ArticleThe Journal of clinical investigation2018
DNA methyltransferase expression in triple-negative breast cancer predicts sensitivity to decitabine.
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 129 papers, 2 of them syntheses that pooled it.
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
129 citing papers in PubMed, 2 syntheses or guidelines pooled it, 207 citations in OpenAlex.
- Pooled it
- A systematic review of progress toward unlocking the power of epigenetics in breast cancer: latest updates and perspectives.Frontiers in pharmacology · 2025Pooled it
- Article
- DNA Hypomethylation Is Not Cell Intrinsically Toxic to Polycomb Repressive Complex 2 Deficient Malignant Peripheral Nerve Sheath Tumors.Genes, chromosomes & cancer · 2026Article
- Review
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- The Great Potential of DNA Methylation in Triple-Negative Breast Cancer: From Biological Basics to Clinical Application.Biomedicines · 2026Review
- Decitabine Induces Subtype-Specific Epigenomic Remodeling and Perturbs Age-Associated Regulatory CpGs in Breast Cancer.Cancer informatics · 2026Article
- Decitabine promotes degradation of DNMT1 and EZH2 via the ubiquitination pathway and inhibits colorectal cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Article
- Review
- Review
- GPM6B inhibits tumor progression by targeting HPGD in lung adenocarcinoma.Molecular medicine reports · 2025Article
- Plasma DNMT1 Activity for Assessing Tumor Burden and Predicting Neoadjuvant Therapy Response in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Structure-Activity Relationship Studies of DNA Methyltransferase 1 Monovalent Degraders.Journal of medicinal chemistry · 2025Article
- The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- Stemness of Cancer: A Study of Triple-negative Breast Cancer From a Neuroscience Perspective.Stem cell reviews and reports · 2025Review
- GSH/pH-responsive copper-based cascade nanocomplexes inducing immunogenic cell death through cuproptosis/ferroptosis/necroptosis in oral squamous cell carcinoma.Materials today. Bio · 2025Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous disease with poor prognosis that lacks targeted therapies, especially in patients with chemotherapy-resistant disease. Since DNA methylation-induced silencing of tumor suppressors is common in cancer, reversal of promoter DNA hypermethylation by 5-aza-2'-deoxycytidine (decitabine), an FDA-approved DNA methyltransferase (DNMT) inhibitor, has proven effective in treating hematological neoplasms. However, its antitumor effect varies in solid tumors, stressing the importance of identifying biomarkers predictive of therapeutic response. Here, we focused on the identification of biomarkers to select decitabine-sensitive TNBC through increasing our understanding of the mechanism of decitabine action. We showed that protein levels of DNMTs correlated with response to decitabine in patient-derived xenograft (PDX) organoids originating from chemotherapy-sensitive and -resistant TNBCs, suggesting DNMT levels as potential biomarkers of response. Furthermore, all 3 methytransferases, DNMT1, DNMT3A, and DNMT3B, were degraded following low-concentration, long-term decitabine treatment both in vitro and in vivo. The DNMT proteins could be ubiquitinated by the E3 ligase, TNF receptor-associated factor 6 (TRAF6), leading to lysosome-dependent protein degradation. Depletion of TRAF6 blocked decitabine-induced DNMT degradation, conferring resistance to decitabine. Our study suggests a potential mechanism of regulating DNMT protein degradation and DNMT levels as response biomarkers for DNMT inhibitors in TNBCs.
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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.