ArticleNature communications2022
Enhancer decommissioning by MLL4 ablation elicits dsRNA-interferon signaling and GSDMD-mediated pyroptosis to potentiate anti-tumor immunity.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Gasdermin D antagonizes immunosuppression in prostate cancer by inducing LAMC2 degradation to block M2 macrophage polarization.Journal for immunotherapy of cancer · 2026Article
- The histone demethylase KDM4A promotes esophageal cancer progression by epigenetically activating LRG1-mediated TGF-β signaling.Apoptosis : an international journal on programmed cell death · 2026Article
- Review
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Mechanistic insights into gasdermin-mediated pyroptosis.Nature reviews. Molecular cell biology · 2025Review
- Efficacy and potential mechanisms of jatrorrhizine on MNNG-induced chronic atrophic gastritis in rats based on serological metabolomics and molecular docking.Scientific reports · 2025Article
- The transcription factor PITX1 cooperates with super-enhancers to regulate the expression of DUSP4 and inhibit pyroptosis in pulmonary artery smooth muscle cells.Respiratory research · 2025Article
- Enhancer reprogramming: critical roles in cancer and promising therapeutic strategies.Cell death discovery · 2025Review
- GSDMD-mediated pyroptosis: molecular mechanisms, diseases and therapeutic targets.Molecular biomedicine · 2025Review
- Gasdermin D regulates the activation of EGFR in colorectal cancer.Journal of translational medicine · 2024Article
- Active enhancers: recent research advances and insights into disease.Biology direct · 2024Review
- Gene Expression Regulation and the Signal Transduction of Programmed Cell Death.Current issues in molecular biology · 2024Review
- Epigenetic regulation of tumor immunity.The Journal of clinical investigation · 2024Review
- The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024Review
- Cell Death Pathway Regulation by Functional Nanomedicines for Robust Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Molecular mechanism of PARP inhibitor resistance.Oncoscience · 2024Review
- Somatic mutations of MLL4/COMPASS induce cytoplasmic localization providing molecular insight into cancer prognosis and treatment.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment.Experimental hematology & oncology · 2023Review
- Gasdermin D: A Potential New Auxiliary Pan-Biomarker for the Detection and Diagnosis of Diseases.Biomolecules · 2023Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Enhancer deregulation is a well-established pro-tumorigenic mechanism but whether it plays a regulatory role in tumor immunity is largely unknown. Here, we demonstrate that tumor cell ablation of mixed-lineage leukemia 3 and 4 (MLL3 and MLL4, also known as KMT2C and KMT2D, respectively), two enhancer-associated histone H3 lysine 4 (H3K4) mono-methyltransferases, increases tumor immunogenicity and promotes anti-tumor T cell response. Mechanistically, MLL4 ablation attenuates the expression of RNA-induced silencing complex (RISC) and DNA methyltransferases through decommissioning enhancers/super-enhancers, which consequently lead to transcriptional reactivation of the double-stranded RNA (dsRNA)-interferon response and gasdermin D (GSDMD)-mediated pyroptosis, respectively. More importantly, we reveal that both the dsRNA-interferon signaling and GSDMD-mediated pyroptosis are of critical importance to the increased anti-tumor immunity and improved immunotherapeutic efficacy in MLL4-ablated tumors. Thus, our findings establish tumor cell enhancers as an additional layer of immune evasion mechanisms and suggest the potential of targeting enhancers or their upstream and/or downstream molecular pathways to overcome immunotherapeutic resistance in cancer patients.
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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.