ArticleFrontiers in cell and developmental biology2021
Pharmacological Targeting of STING-Dependent IL-6 Production in Cancer Cells.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Carnosic Acid Activates the STING/IRF3 Pathway to Induce Nitric Oxide-Mediated Apoptosis in Osteosarcoma Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Chronic and non-canonical cGAS-STING activation: implications for health, disease, cancer, and emerging therapeutic opportunities.Apoptosis : an international journal on programmed cell death · 2026Review
- The cGAS-STING pathway in cancer immunotherapy: prognostic value and therapeutic potential.Frontiers in immunology · 2026Review
- Endothelial Cell Stimulator of Interferon Genes Regulates IL-6 Production and Is Required for Pathologic Cardiac Hypertrophy and Contractile Dysfunction in Experimental Heart Failure.The American journal of pathology · 2025Article
- Dual-Action Tocilizumab-Conjugated Cisplatin Nanoparticles Overcome Chemoresistance and Metastasis in Non-Small-Cell Lung Cancer.Pharmaceutics · 2025Article
- Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment.Molecular cancer · 2025Review
- The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications.Journal of hematology & oncology · 2025Review
- Article
- Advances in radiotherapy enhancing the efficacy of immune checkpoint inhibitors in malignant.Frontiers in oncology · 2025Review
- Recent advances in targeting the cGAS-STING pathway for immunotherapy in orthopedic diseases.Frontiers in immunology · 2025Review
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- The balance of STING signaling orchestrates immunity in cancer.Nature immunology · 2024Review
- NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia.International journal of molecular sciences · 2024Article
- IFNλ1 is a STING-dependent mediator of DNA damage and induces immune activation in lung cancer.Frontiers in immunology · 2024Article
- At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Induction of Inflammation Disrupts the Negative Interplay between STING and S1P Axis That Is Observed during Physiological Conditions in the Lung.International journal of molecular sciences · 2023Article
- The cGAS-STING Pathway Affects Vertebral Bone but Does Not Promote Intervertebral Disc Cell Senescence or Degeneration.Frontiers in immunology · 2022Article
- Systemic benefit of radiation therapyFrontiers in oncology · 2022Article
- Cancer immunotherapy strategies that target the cGAS-STING pathway.Frontiers in immunology · 2022Review
- Inhibitory targeting cGAS-STING-TBK1 axis: Emerging strategies for autoimmune diseases therapy.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the STING pathway upon genotoxic treatment of cancer cells has been shown to lead to anti-tumoral effects, mediated through the acute production of interferon (IFN)-β. Conversely, the pathway also correlates with the expression of NF-κB-driven pro-tumorigenic genes, but these associations are only poorly defined in the context of genotoxic treatment, and are thought to correlate with a chronic engagement of the pathway. We demonstrate here that half of the STING-expressing cancer cells from the NCI60 panel rapidly increased expression of pro-tumorigenic IL-6 upon genotoxic DNA damage, often independent of type-I IFN responses. While preferentially dependent on canonical STING, we demonstrate that genotoxic DNA damage induced by camptothecin (CPT) also drove IL-6 production through non-canonical STING signaling in selected cancer cells. Consequently, pharmacological inhibition of canonical STING failed to broadly inhibit IL-6 production induced by CPT, although this could be achieved through downstream ERK1/2 inhibition. Finally, prolonged inhibition of canonical STING signaling was associated with increased colony formation of MG-63 cells, highlighting the duality of STING signaling in also restraining the growth of selected cancer cells. Collectively, our findings demonstrate that genotoxic-induced DNA damage frequently leads to the rapid production of pro-tumorigenic IL-6 in cancer cells, independent of an IFN signature, through canonical and non-canonical STING activation; this underlines the complexity of STING engagement in human cancer cells, with frequent acute pro-tumorigenic activities induced by DNA damage. We propose that inhibition of ERK1/2 may help curb such pro-tumorigenic responses to DNA-damage, while preserving the anti-proliferative effects of the STING-interferon axis.
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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.