ArticleProceedings of the National Academy of Sciences of the United States of America2014
Human breast cancer metastases to the brain display GABAergic properties in the neural niche.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 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
235 citing papers in PubMed, 347 citations in OpenAlex.
- Neural-tumor interactions: bidirectional regulatory mechanisms and nervous system-targeted tumor therapeutic strategies.Biomarker research · 2026Review
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Spatially resolved transcriptomics in human brain metastases identifies macrophage-tumor interactions associated with survival.iScience · 2026Article
- Circular RNA dynamics in breast-to-brain metastatic cascade.BMC biology · 2026Article
- GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells.Nature cancer · 2026Article
- Investigating GSK-3β as a Potential Prognostic Marker for Metastasis in Head and Neck Squamous Cell Carcinoma: A Preliminary Study on the Crossroads of GABAergic and Wnt Signaling.European journal of dentistry · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Deciphering the Role of Cancer Stem Cells in Breast Cancer Brain Colonization Using a Novel Patient-Derived Model.Advanced healthcare materials · 2026Article
- Single-cell profiling reveals distinct populations of tumor-associated macrophages and metastatic tumor cells in breast cancer brain metastasis.Cell death & disease · 2026Article
- Review
- Targeting the neuro-immune crosstalk in breast cancer brain metastases.Journal for immunotherapy of cancer · 2026Review
- Targeting immunosuppressive network in glioblastoma: Emerging strategies to overcome immunodeficiency and enhance therapeutic efficacy.Acta pharmaceutica Sinica. B · 2026Review
- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
- Breast Cancer Brain Metastases: Current Understanding and Future Directions.Current oncology reports · 2026Review
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer.International journal of biological sciences · 2026Article
- Exploring the Neurobiological Mechanisms of Cancer Growth.Current pharmaceutical design · 2026Review
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
- Neural regulation of immune evasion in breast cancer: a multiscale neuro-immune framework.Frontiers in immunology · 2026Review
175 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Dispersion of tumors throughout the body is a neoplastic process responsible for the vast majority of deaths from cancer. Despite disseminating to distant organs as malignant scouts, most tumor cells fail to remain viable after their arrival. The physiologic microenvironment of the brain must become a tumor-favorable microenvironment for successful metastatic colonization by circulating breast cancer cells. Bidirectional interplay of breast cancer cells and native brain cells in metastasis is poorly understood and rarely studied. We had the rare opportunity to investigate uncommonly available specimens of matched fresh breast-to-brain metastases tissue and derived cells from patients undergoing neurosurgical resection. We hypothesized that, to metastasize, breast cancers may escape their normative genetic constraints by accommodating and coinhabiting the neural niche. This acquisition or expression of brain-like properties by breast cancer cells could be a malignant adaptation required for brain colonization. Indeed, we found breast-to-brain metastatic tissue and cells displayed a GABAergic phenotype similar to that of neuronal cells. The GABAA receptor, GABA transporter, GABA transaminase, parvalbumin, and reelin were all highly expressed in breast cancer metastases to the brain. Proliferative advantage was conferred by the ability of breast-to-brain metastases to take up and catabolize GABA into succinate with the resultant formation of NADH as a biosynthetic source through the GABA shunt. The results suggest that breast cancers exhibit neural characteristics when occupying the brain microenvironment and co-opt GABA as an oncometabolite.
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.