ArticleNature2016
Carcinoma-astrocyte gap junctions promote brain metastasis by cGAMP transfer.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 635 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
635 citing papers in PubMed, 918 citations in OpenAlex.
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- Review
- Review
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- A versatile cGAMP reporter reveals principles of cGAS activation by DNA damage and chromosome instability.Nature cell biology · 2026Article
- Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.Medical oncology (Northwood, London, England) · 2026Review
- The cGAS-STING pathway in inflammaging and neuroinflammation.Science China. Life sciences · 2026Review
- The Invasive Margin of Glioblastoma as a Molecular Ecosystem: Spatial Heterogeneity, Tumor-Host Interactions, and Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- cGAS-STING pathway activation drives the cold-to-hot tumor transition and sensitizes immunotherapy.Cancer biology & medicine · 2026Review
- Residual Lung Cancer After Incomplete Microwave Ablation Exhibits cGAS-STING-ZEB1-Driven Malignant Progression.Cancers · 2026Article
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- The cGAS/STING pathway in cancer: translating innate DNA sensing into therapeutic potential.The Journal of clinical investigation · 2026Review
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- Astrocyte heterogeneity in brain metastases.Molecular oncology · 2026Review
- [Mechanisms of cGAS-STING-mediated chronic inflammation and targeted interventions in brain aging].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- [Tumor Cell and Brain Microenvironment Interactions in Non-small Cell Lung Cancer Brain Metastasis: Mechanisms and Emerging Insights].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Role of Connexin-43: from cancer initiation to cancer metastasis.Molecular biology reports · 2026Review
- Therapeutic targeting of the cGAS-STING pathway in human disease.The Journal of clinical investigation · 2026Review
- Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).International journal of molecular medicine · 2026Review
- Multiscale systems modelling of communication networks in brain metastasis.Experimental & molecular medicine · 2026Review
575 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Brain metastasis represents a substantial source of morbidity and mortality in various cancers, and is characterized by high resistance to chemotherapy. Here we define the role of the most abundant cell type in the brain, the astrocyte, in promoting brain metastasis. We show that human and mouse breast and lung cancer cells express protocadherin 7 (PCDH7), which promotes the assembly of carcinoma-astrocyte gap junctions composed of connexin 43 (Cx43). Once engaged with the astrocyte gap-junctional network, brain metastatic cancer cells use these channels to transfer the second messenger cGAMP to astrocytes, activating the STING pathway and production of inflammatory cytokines such as interferon-α (IFNα) and tumour necrosis factor (TNF). As paracrine signals, these factors activate the STAT1 and NF-κB pathways in brain metastatic cells, thereby supporting tumour growth and chemoresistance. The orally bioavailable modulators of gap junctions meclofenamate and tonabersat break this paracrine loop, and we provide proof-of-principle that these drugs could be used to treat established brain metastasis.
Indexed as
Identifiers
What OpenQuestion holds
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.