ArticleJournal of immunology (Baltimore, Md. : 1950)2015
H3K9 Trimethylation Silences Fas Expression To Confer Colon Carcinoma Immune Escape and 5-Fluorouracil Chemoresistance.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 109 citations in OpenAlex.
- Colorectal cancer landscape from gut microbiota: Insights into mutations, epigenetic dysregulation, and immune microenvironment alterations.Virulence · 2026Review
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Arginine methylation-dependent stabilization of SUV39H1 promotes breast cancer growth.Oncogene · 2026Article
- Targeting cell death: a promising approach for colorectal cancer therapy.Cancer cell international · 2026Review
- Total Synthesis and Anticancer Study of (+)-Verticillin A.Journal of the American Chemical Society · 2025Article
- Slc7a5 promotes T cell anti-tumor immunity through sustaining cytotoxic T lymphocyte effector function.Oncogene · 2025Article
- Studies on the epipolythiodioxopiperazine alkaloid verticillin D: Scaled production, streamlined purification, and absolute configuration.Phytochemistry · 2025Article
- Histone H3K9 Methylation Is Differentially Modified in Odontogenic Cyst and Tumors.European journal of dentistry · 2025Article
- Verticillin A-Loaded Surgical Buttresses Prevent Local Pancreatic Cancer Recurrence in a Murine Model.Molecular pharmaceutics · 2025Article
- The Roles of H3K9me3 Writers, Readers, and Erasers in Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Verticillins: fungal epipolythiodioxopiperazine alkaloids with chemotherapeutic potential.Natural product reports · 2024Review
- β-hydroxybutyrate resensitizes colorectal cancer cells to oxaliplatin by suppressing H3K79 methylation in vitro and in vivo.Molecular medicine (Cambridge, Mass.) · 2024Article
- The effects of metabolism on the immune microenvironment in colorectal cancer.Cell death discovery · 2024Review
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- Synthesis and Biological Evaluation of Novel Uracil Derivatives as Thymidylate Synthase Inhibitors.Applied biochemistry and biotechnology · 2023Article
- Targeting drug-tolerant cells: A promising strategy for overcoming acquired drug resistance in cancer cells.MedComm · 2023Review
- Exploration of Verticillins in High-Grade Serous Ovarian Cancer and Evaluation of Multiple Formulations in Preclinical In Vitro and In Vivo Models.Molecular pharmaceutics · 2023Article
- Selenylated Imidazo [1,2-Pharmaceuticals (Basel, Switzerland) · 2023Article
- HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer.PLoS pathogens · 2023Article
- Epipolythiodioxopiperazine-Based Natural Products: Building Blocks, Biosynthesis and Biological Activities.Chembiochem : a European journal of chemical biology · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
The Fas-FasL effector mechanism plays a key role in cancer immune surveillance by host T cells, but metastatic human colon carcinoma often uses silencing Fas expression as a mechanism of immune evasion. The molecular mechanism under FAS transcriptional silencing in human colon carcinoma is unknown. We performed genome-wide chromatin immunoprecipitation sequencing analysis and identified that the FAS promoter is enriched with H3K9me3 in metastatic human colon carcinoma cells. The H3K9me3 level in the FAS promoter region is significantly higher in metastatic than in primary cancer cells, and it is inversely correlated with Fas expression level. We discovered that verticillin A is a selective inhibitor of histone methyltransferases SUV39H1, SUV39H2, and G9a/GLP that exhibit redundant functions in H3K9 trimethylation and FAS transcriptional silencing. Genome-wide gene expression analysis identified FAS as one of the verticillin A target genes. Verticillin A treatment decreased H3K9me3 levels in the FAS promoter and restored Fas expression. Furthermore, verticillin A exhibited greater efficacy than decitabine and vorinostat in overcoming colon carcinoma resistance to FasL-induced apoptosis. Verticillin A also increased DR5 expression and overcame colon carcinoma resistance to DR5 agonist drozitumab-induced apoptosis. Interestingly, verticillin A overcame metastatic colon carcinoma resistance to 5-fluorouracil in vitro and in vivo. Using an orthotopic colon cancer mouse model, we demonstrated that tumor-infiltrating cytotoxic T lymphocytes are FasL(+) and that FasL-mediated cancer immune surveillance is essential for colon carcinoma growth control in vivo. Our findings determine that H3K9me3 of the FAS promoter is a dominant mechanism underlying FAS silencing and resultant colon carcinoma immune evasion and progression.
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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.