ArticleNature2019
Synaptic proximity enables NMDAR signalling to promote brain metastasis.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 360 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Repurposing the Antipsychotic Drug Chlorpromazine as a Therapeutic Agent in the Combined Treatment of Newly Diagnosed Glioblastoma Multiforme
Glutamate Excitotoxicity in Brain Metastases From Lung, Breast and Melanoma Treated With Stereotactic Radiosurgery
Who cites it
360 citing papers in PubMed, 1 synthesis or guideline pooled it, 530 citations in OpenAlex.
- Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.International journal of molecular sciences · 2023Pooled it
- Neuro-associated SEMA3CClinical and translational medicine · 2026Article
- The emerging roles of cerebral pericytes in brain metastasis.Neuro-oncology · 2026Review
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- Neural regulation of cancer: from microenvironmental hijacking to systemic circuit co-option.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Metabolic adaptations of the tumor macroenvironment and their role in cancer progression and survivorship.Genes & development · 2026Review
- Targeting Wild-type NTRK in NTRK Fusion-Negative Lung Cancer Decreases Brain Metastases.Cancer research communications · 2026Article
- Breast cancer ovarian metastases show increased activity of GPCR pathways.bioRxiv : the preprint server for biology · 2026Article
- Neural regulation of cancer: from synaptic integration to neuro-immune regulation.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Single-cell and spatial transcriptomes reveal oligodendrocyte remodeling fatty acid metabolism microenvironment of lung cancer brain metastases.Journal of translational medicine · 2026Article
- Distinct Malignant Cell States and Myeloid Glutamate Signaling Associated with Aggressive Pancreatic Neuroendocrine Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- The metabolic plasticity of cancer stem cells: bidirectional crosstalk with organ-resident cells.Experimental & molecular medicine · 2026Review
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Transsynaptic tracing techniques to interrogate neuronal connectivity of glioblastomas.Nature protocols · 2026Review
- Brain FGF2 and NCAM1 contribute to FGFR1-dependent progression of estrogen receptor-positive breast cancer brain metastases.Nature communications · 2026Article
- Adenosine Signaling in Primary and Metastatic Brain Tumors: Immune Suppression, Tumor Progression, and Therapeutic Opportunities.Molecular neurobiology · 2026Review
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Dissecting acute neuronal responses to glioblastoma using a dual-interface human iPSC neuronal culture platform.Acta neuropathologica communications · 2026Article
300 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Metastasis-the disseminated growth of tumours in distant organs-underlies cancer mortality. Breast-to-brain metastasis (B2BM) is a common and disruptive form of cancer and is prevalent in the aggressive basal-like subtype, but is also found at varying frequencies in all cancer subtypes. Previous studies revealed parameters of breast cancer metastasis to the brain, but its preference for this site remains an enigma. Here we show that B2BM cells co-opt a neuronal signalling pathway that was recently implicated in invasive tumour growth, involving activation by glutamate ligands of N-methyl-D-aspartate receptors (NMDARs), which is key in model systems for metastatic colonization of the brain and is associated with poor prognosis. Whereas NMDAR activation is autocrine in some primary tumour types, human and mouse B2BM cells express receptors but secrete insufficient glutamate to induce signalling, which is instead achieved by the formation of pseudo-tripartite synapses between cancer cells and glutamatergic neurons, presenting a rationale for brain metastasis.
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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.