ArticleApoptosis : an international journal on programmed cell death2022
DNA damage induces STING mediated IL-6-STAT3 survival pathway in triple-negative breast cancer cells and decreased survival of breast cancer patients.
Article in Apoptosis : an international journal on programmed cell death, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- The efficacy of angiogenesis inhibitors combined with chemotherapy in advanced breast cancer: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- Multi-omics graph attention network reveals neuro-immune-tumor pathways in breast cancer liver depression syndrome.Frontiers in immunology · 2026Trial
- From initial complete response to recurrence: ENPP1 mutation drives cisplatin resistance through STING/NF-κB/IL-6 axis in hypopharyngeal squamous cell carcinoma.British journal of cancer · 2026Article
- Dynamic phosphorylation of cGAS by DNA-PKcs and PPP1CC balances DNA repair and innate immunity.Medical oncology (Northwood, London, England) · 2026Article
- Differential Expression of hsa-miR-34c-5p, hsa-miR-200b-3p, hsa-miR-320a-3p and Their Target Genes Determine Survival in Clear-Cell Renal Cell Carcinoma.Annals of surgical oncology · 2026Article
- Decoding triple negative breast cancer bone metastasis: from 3D bioprinted models to clinical translation.Journal of nanobiotechnology · 2026Review
- Doxorubicin-Induced Cardiotoxicity in Breast Cancer: Mechanistic Pathways, Pharmacogenomic Modifiers, and Translational Strategies.Cardiovascular toxicology · 2026Review
- JAK/STAT-mediated regulation of PD-L1 expression in breast cancer: Molecular mechanisms and implications for immunotherapy.iScience · 2026Review
- Low-dose radiotherapy remodels the tumor immune microenvironment via the cGAS-STING pathway: mechanisms, challenges, and combination therapy strategies.Molecular cancer · 2026Review
- 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
- Photothermal therapy triggering organelle stress and metabolic reprogramming to potentiate antitumor immunity.Frontiers in immunology · 2026Review
- Bridging innate immunity and iron-dependent death: the interplay between cyclic GMP-AMP synthase-stimulator of interferon genes nexus and ferroptosis in cancer and inflammation.Frontiers in cell and developmental biology · 2026Review
- HNRNPA2B1 confers immune escape of non-small cell lung cancer through targeting lactate/ferroptosis.Cell death & disease · 2025Article
- IRE1α translational suppression potentiates STING-dependent chemoresistance in pancreatic cancer.Cell death & disease · 2025Article
- Modeling and targeting general and chromosome-specific aneuploidy in cancer.Genes & development · 2025Review
- Nanocarrier-mediated modulation of cGAS-STING signaling pathway to disrupt tumor microenvironment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Silibinin Anticancer Effects Through the Modulation of the Tumor Immune Microenvironment in Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment.Molecular cancer · 2025Review
- The cGAS-STING axis: a comprehensive review from immune defense to disease pathogenesis.Immunologic research · 2025Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple-negative breast cancer is aggressive and metastatic breast cancer type and shows immune evasion, drug resistance, relapse and poor survival. Anti-cancer therapy like ionizing radiation and chemotherapeutic drug majorly induces DNA damage hence, alteration in DNA damage repair and downstream pathways may contribute to tumor cell survival. DNA damage during chemotherapy is sensed by cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes (STING), which determines the anti-tumor immune response by modulating the expression of programmed cell death ligand-1 (PD-L1), immune suppressor, in the tumor microenvironment. Triple-negative breast cancer cells are cGAS-STING positive and modulation of this pathway during DNA damage response for survival and immune escape mechanism is not well understood. Here we demonstrate that doxorubicin-mediated DNA damage induces STING mediated NF-κB activation in triple-negative as compared to ER/PR positive breast cancer cells. STING-mediated NF-κB induces the expression of IL-6 in triple-negative breast cancer cells and activates pSTAT3, which enhances cell survival and PD-L1 expression. Doxorubicin and STAT3 inhibitor act synergistically and inhibit cell survival and clonogenicity in triple-negative breast cancer cells. Knockdown of STING in triple-negative breast cancer cells enhances CD8 mediated immune cell death of breast cancer cells. The combinatorial treatment of triple-negative breast cells with doxorubicin and STAT3 inhibitor reduces PD-L1 expression and activates immune cell-mediated cancer cell death. Further STING and IL-6 levels show a positive correlation in breast cancer patients and poor survival outcomes. The study here strongly suggests that STING mediated activation of NF-κB enhances IL-6 mediated STAT3 in triple-negative breast cancer cells which induces cell survival and immune-suppressive mechanism.
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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.