ArticleScience advances2024
Select EZH2 inhibitors enhance viral mimicry effects of DNMT inhibition through a mechanism involving NFAT:AP-1 signaling.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 25 citations in OpenAlex.
- Hsa_circ_0000711 can serve as a novel biomarker for primary biliary cholangitis by promoting disease progression through the regulation of miR-185-5p and NFATc3.RNA biology · 2026Article
- Targeting the DNA Damage Response in Cancer.MedComm · 2026Review
- Review
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- Article
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Targeting the Epigenome in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Targeting EZH2-driven cholesterol metabolic vulnerability through Napabucasin suppresses ovarian cancer metastasis.Cell death & disease · 2026Article
- Reduced Maintenance DNA Methylation Thresholds Enable Sensitive Reporter Assays for UHRF1 and DNMT1 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- RETRACTED: Endogenous Retroviruses as Regulators of Innate Immune Signaling and InflammationViruses · 2026Review
- Crosstalk between EZH2 and DNA methylation mediates neuroendocrine prostate cancer lineage plasticity.Nature communications · 2026Article
- Biomarker guided combination strategies and perioperative integration for immune cold microsatellite stable colorectal cancer.Discover oncology · 2026Review
- Roles of different methylation modifications in cardiovascular disease.Frontiers of medicine · 2025Review
- Epigenetic drugs in cancer therapy: mechanisms, immune modulation, and therapeutic applications.Molecular biomedicine · 2025Review
- Dual EZH1/2 inhibition enhances DNMT inhibitor efficacy in colon cancer through targeting H3K27me1.bioRxiv : the preprint server for biology · 2025Article
- DNA methylation and transcription factor-driven immune subtypes in ovarian cancer.Discover oncology · 2025Article
- Prognostic Significance ofCancer genomics & proteomics · 2025Article
- EZH2 inhibition and 5-azacytidine enhance antitumor immunity in PTEN-deficient glioblastoma by activation viral mimicry response.Journal for immunotherapy of cancer · 2025Article
- Dual Targeting EZH2 and Histone Deacetylases in Human Uterine Sarcoma Cells Under Both 2D and 3D Culture Conditions.Journal of cellular and molecular medicine · 2025Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
DNA methyltransferase inhibitor (DNMTi) efficacy in solid tumors is limited. Colon cancer cells exposed to DNMTi accumulate lysine-27 trimethylation on histone H3 (H3K27me3). We propose this Enhancer of Zeste Homolog 2 (EZH2)-dependent repressive modification limits DNMTi efficacy. Here, we show that low-dose DNMTi treatment sensitizes colon cancer cells to select EZH2 inhibitors (EZH2is). Integrative epigenomic analysis reveals that DNMTi-induced H3K27me3 accumulates at genomic regions poised with EZH2. Notably, combined EZH2i and DNMTi alters the epigenomic landscape to transcriptionally up-regulate the calcium-induced nuclear factor of activated T cells (NFAT):activating protein 1 (AP-1) signaling pathway. Blocking this pathway limits transcriptional activating effects of these drugs, including transposable element and innate immune response gene expression involved in viral defense. Analysis of primary human colon cancer specimens reveals positive correlations between DNMTi-, innate immune response-, and calcium signaling-associated transcription profiles. Collectively, we show that compensatory EZH2 activity limits DNMTi efficacy in colon cancer and link NFAT:AP-1 signaling to epigenetic therapy-induced viral mimicry.
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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.