ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Inactivated cGAS-STING Signaling Facilitates Endocrine Resistance by Forming a Positive Feedback Loop with AKT Kinase in ER+HER2- Breast Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Spatial transcriptomics in cancer research: insights into tumorigenesis, diagnosis and therapeutics.Cell death discovery · 2026Review
- A-to-I RNA Editing Endows miR-3664-5p with Carcinogenicity in Breast Cancer Through Modulating LONP2 Mediated Glycolysis.Journal of mammary gland biology and neoplasia · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Endocrine Resistance Score Based on Three Key Genes Predicts Prognosis and Reveals Potential Therapeutic Targets for ER+HER2- Breast Cancer.Cell proliferation · 2026Article
- Nanomedicine leverages cuproptosis-mediated cGAS-STING activation to enhance antitumor immunity.Journal of nanobiotechnology · 2026Review
- GNAL-driven calcium signaling reshapes the spatiotemporal immune landscape in ERTranslational cancer research · 2026Article
- The role of the intratumoral microbiota in breast cancer metastasis and immune regulation: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- The cGAS-STING pathway in cancer immunotherapy: prognostic value and therapeutic potential.Frontiers in immunology · 2026Review
- The cGAS-STING pathway in tumor immunity: dual roles, regulatory mechanisms, and precision therapeutic strategies.Frontiers in pharmacology · 2026Review
- Quercetin Alleviates Osteoarthritis Pain by Inhibiting Vascular Endothelial Growth Factor A Through Regulating cGAS/STING Pathway.Journal of cellular and molecular medicine · 2026Article
- cGAS-STING and PANoptosis: Interplay, Underlying Mechanisms, and Therapeutic Targets.Drug design, development and therapy · 2026Review
- Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- DOT1L inhibition exerts the anti-tumor effect by activating interferon signaling in breast cancer cells.Clinical epigenetics · 2025Article
- Targeting the interplay of cGAS-STING and ferroptosis by nanomedicine in the treatment of cancer.Journal of experimental & clinical cancer research : CR · 2025Review
- Cancer therapy resistance from a spatial-omics perspective.Clinical and translational medicine · 2025Review
- Article
- The Rab18/Ras/ERK/FosB/MMP3 Signaling Pathway Mediates Cell Migration Regulation by 2'3'-cGAMP.International journal of molecular sciences · 2025Article
- Cyclic GMP-AMP Synthase (cGAS) Deletion Promotes Less Prominent Inflammatory Macrophages and Sepsis Severity in Catheter-Induced Infection and LPS Injection Models.International journal of molecular sciences · 2025Article
- Reprogramming tumor-associated macrophages using STING or TLR agonists: a promising strategy to enhance immunotherapy in hormone-dependent cancers.Journal for immunotherapy of cancer · 2025Review
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Authors and funding
19 authors.
Funding
Abstract
Endocrine-resistant ER+HER2- breast cancer (BC) is particularly aggressive and leads to poor clinical outcomes. Effective therapeutic strategies against endocrine-resistant BC remain elusive. Here, analysis of the RNA-sequencing data from ER+HER2- BC patients receiving neoadjuvant endocrine therapy and spatial transcriptomics analysis both show the downregulation of innate immune signaling sensing cytosolic DNA, which primarily occurs in endocrine-resistant BC cells, not immune cells. Indeed, compared with endocrine-sensitive BC cells, the activity of sensing cytosolic DNA through the cGAS-STING pathway is attenuated in endocrine-resistant BC cells. Screening of kinase inhibitor library show that this effect is mainly mediated by hyperactivation of AKT1 kinase, which binds to kinase domain of TBK1, preventing the formation of a trimeric complex TBK1/STING/IRF3. Notably, inactivation of cGAS-STING signaling forms a positive feedback loop with hyperactivated AKT1 to promote endocrine resistance, which is physiologically important and clinically relevant in patients with ER+HER2- BC. Blocking the positive feedback loop using the combination of an AKT1 inhibitor with a STING agonist results in the engagement of innate and adaptive immune signaling and impairs the growth of endocrine-resistant tumors in humanized mice models, providing a potential strategy for treating patients with endocrine-resistant BC.
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