ArticleCell reports2023
SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.
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Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
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25 citing papers in PubMed, 24 citations in OpenAlex.
- Targeting the DNA-repair chromatin-modifier protein SMYD3 as a novel epigenetics-based therapy for gastric cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Predictive bioactivity modeling and structural binding analysis for the identification of potential SMYD3 modulators.Molecular diversity · 2026Article
- Review
- METTL3 Methylation Induces Decay of Endogenous Retroelement Transcripts to Promote Tumor Immune Evasion.Cancer research · 2026Article
- Review
- SMYD3-CDCP1 Axis Drives EMT and CAF Activation in Colorectal Cancer and Is Targetable for Oxaliplatin Sensitization.Biomedicines · 2025Article
- Uncovering chromatin factor landscapes in head and neck squamous cell carcinoma.Oral oncology · 2025Article
- Oncogenic and immunomodulatory functions of SUV420H1 in HPV-negative head and neck squamous cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Turning cold tumors into hot tumors to ignite immunotherapy.Molecular cancer · 2025Review
- Bifaceted functions of histone methyltransferases.Epigenomics · 2025Article
- Improvement of the Anticancer Efficacy of PD-1/PD-L1 Blockade: Advances in Molecular Mechanisms and Therapeutic Strategies.MedComm · 2025Review
- Uhrf1 downregulation promotes β-cell dedifferentiation by decreasing Foxo1 expression in type 2 diabetes.Journal of diabetes investigation · 2025Article
- UHRF1 in Immune Regulation and Diseases: Mechanisms and Therapeutic Implications.Clinical reviews in allergy & immunology · 2025Review
- SMYD3 drives cell cycle and epithelial-mesenchymal transition pathways through dual gene transcriptional repression and activation in HPV-negative head and neck cancer.Scientific reports · 2025Article
- Molecular insights into immune evasion in head and neck squamous cell carcinomas: Toward a promising treatment strategy.Oncology research · 2025Review
- SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance.Experimental & molecular medicine · 2024Review
- The Roles of H3K9me3 Writers, Readers, and Erasers in Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Chemoprevention of Head and Neck Cancer: A Review of Current Approaches and Future Perspectives.Cancer prevention research (Philadelphia, Pa.) · 2024Review
- Smyd3-mediated immuno-modulation in HPV-negative head and neck squamous cell carcinoma mouse models.iScience · 2024Article
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
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Authors and funding
38 authors at 11 institutions in 2 countries.
Nupur NigamThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Benjamin BernardThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Samantha SevillaCollaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Sohyoung KimLaboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD 20892, USA.
Mohd Saleem DarThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Daniel TsaiThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Yvette RobbinsTranslational Tumor Immunology Program, NIDCD, NIH, Bethesda, MD 20892, USA.
Kyunghee BurkittThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Cem SieversTranslational Tumor Immunology Program, NIDCD, NIH, Bethesda, MD 20892, USA.
Clint T AllenTranslational Tumor Immunology Program, NIDCD, NIH, Bethesda, MD 20892, USA.
Richard L BennettUniversity of Florida Cancer Center, Gainesville, FL 32610, USA.
Theophilus T TetteyLaboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD 20892, USA.
Benjamin CarterNational Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
Lorenzo RinaldiLaboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD 20892, USA.
Mark W LingenUniversity of Chicago, Department of Pathology, Chicago, IL 60637, USA.
Houssein SaterGU Malignancies Branch, NCI, NIH, Bethesda, MD 20892, USA.
Elijah F EdmondsonMolecular Histopathology Laboratory, Frederick National Laboratory for Cancer Research, NIH, Frederick, MD 21702, USA.
Arfa MoshiriThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Abbas SaeedThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Hui ChengNational Institute of Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
Xiaolin LuoIonis Pharmaceuticals, Carlsbad, CA 92010, USA.
Kevin BrennanDepartment of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Vishal KopardeCollaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Chen ChenDepartment of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sudipto DasProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD 21702, USA.
Thorkell AndressonProtein Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc, Frederick, MD 21702, USA.
Abdalla AbdelmaksoudCollaborative Bioinformatics Resource, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Madhavi MuraliThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
Seiji SakataPathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-0063, Japan; Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-0063, Japan.
Kengo TakeuchiPathology Project for Molecular Targets, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-0063, Japan; Division of Pathology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo 135-0063, Japan; Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo 135-0063, Japan.
Raj ChariGenome Modification Core, Laboratory Animal Sciences Program, Frederick National Lab for Cancer Research, Frederick, MD 21702, USA.
Yusuke NakamuraCancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo 135-0063, Japan.
Ravindra UppaluriDana Farber Cancer Institute, Boston, MA 02215, USA.
John B SunwooDepartment of Otolaryngology - Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
Carter Van WaesNational Institute of Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
Jonathan D LichtUniversity of Florida Cancer Center, Gainesville, FL 32610, USA.
Gordon L HagerLaboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD 20892, USA.
Vassiliki SalouraThoracic and GI Malignancies Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: vassiliki.saloura@nih.gov.
Center for Cancer Research · USNational Institute on Deafness and Other Communication Disorders · USFrederick National Laboratory for Cancer Research · USJapanese Foundation For Cancer Research · JPStanford University · USLeidos Biomedical Research Inc. (United States)University of Florida Health · USDana-Farber Cancer Institute · USIonis Pharmaceuticals (United States) · USNational Heart Lung and Blood Institute · USUniversity of Chicago · US
Funding
Chromatin Structure and Gene ExpressionZIABC005450 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HAGER, GORDON L · 2009 to 2025
$35.2MThe Role of WHSC1L1 in Squamous Cell Carcinoma of the Head and NeckZIABC011831 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SALOURA, VASSILIKI · 2018 to 2025
$7.6MIntramural NIH HHS ZIA BC011831NCI NIH HHS HHSN261201500003CNCI NIH HHS HHSN261201500003I
Abstract
Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells. Mechanistically, SMYD3 binds to and regulates the transcription of UHRF1, encoding for a reader of H3K9me3, which binds to H3K9me3-enriched promoters of key immune-related genes, recruits DNMT1, and silences their expression. SMYD3 further maintains the repression of immune-related genes through intragenic deposition of H4K20me3. In vivo, Smyd3 depletion induces influx of CD8
Indexed as
Head and Neck NeoplasmsHistone-Lysine N-MethyltransferaseInterferon Type IPapillomavirus InfectionsSquamous Cell Carcinoma of Head and NeckCCAAT-Enhancer-Binding ProteinsCD8-Positive T-LymphocytesHumansUbiquitin-Protein LigasesCCAAT-Enhancer-Binding ProteinsHistone-Lysine N-MethyltransferaseInterferon Type ISMYD3 protein, humanUbiquitin-Protein LigasesUHRF1 protein, humanantitumor immune responseCP: CancerCP: Immunologyhead and neck cancerinterferon responseSMYD3
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