ArticleScience advances2025
SMARCA4 regulates the NK-mediated killing of senescent cells.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Immune surveillance and immune evasion of senescent cells.Nature reviews. Immunology · 2026Review
- The Bidirectional Role of Cellular Senescence in the Treatment of Ovarian Cancer.Biomedicines · 2026Review
- Immunological consequences of senescence in physiology and pathology.Journal of translational medicine · 2026Review
- Distinct multiplex immunofluorescence-based immune and stromal marker expression profile of subcutaneously metastatic SMARCA4-deficient undifferentiated thoracic tumor: a case report.Translational lung cancer research · 2026Article
- Enhanced Anti-Lung Cancer Efficacy of Neo-BCV Combined with Cisplatin: Immune Activation and Tumor Microenvironment Remodeling.Vaccines · 2026Article
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Targeting immunosenescence in lung diseases: mechanistic insights and clinical interventions.BMC medicine · 2026Review
- Targeting the LHX1-LDB1 Complex Restores STING-dependent Senescence Surveillance and Inhibits Head and Neck Cancer Progression.International journal of biological sciences · 2026Article
- The Implications of Radiotherapy-Induced Cellular Senescence for Cancer Treatment and Tumor Microenvironment Modulation.International journal of biological sciences · 2026Review
- Radiosensitization Effect of PARP Inhibitor Talazoparib Involves Decreasing Mitochondrial Membrane Potential and Induction of Cellular Senescence.Current issues in molecular biology · 2025Article
- Review
- Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics.Molecular cancer · 2025Review
- The interplay between senescence, inflammation, and the immune system.Genes & development · 2025Review
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells. We identified that genetic or pharmacological inhibition of SMARCA4 enhanced senescent cell elimination by NK cells. SMARCA4 expression is elevated during senescence and its inhibition derepresses repetitive elements, inducing the SASP via activation of cGAS/STING and MAVS/MDA5 pathways. Moreover, a PROTAC targeting SMARCA4 synergized with cisplatin to increase the infiltration of CD8 T cells and mature, activated NK cells in an immunocompetent model of ovarian cancer. Our results indicate that SMARCA4 inhibitors enhance NK-mediated surveillance of senescent cells and may represent senotherapeutic interventions for ovarian cancer.
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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.