{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:59:50Z","timestamp":1787687990177,"version":"build-2784847793"},"reference-count":171,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009326","name":"Cancer Research Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009326","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00t38a349","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Sciences and Engineering Council of Canada"},{"id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Breast cancer brain metastasis (BCBM) affects up to 30% of patients with metastatic disease and carries a median survival of only 4\u201318 months. Emerging evidence reveals that BCBM cells are not passive survivors, but active participants that hijack core neurotransmitter networks, GABA (gamma-aminobutyric acid) and glutamate, to fuel their growth. BCBM, particularly triple-negative breast cancer (TNBC), frequently switch to a GABAergic mode utilizing brain-derived GABA as an oncometabolite. In parallel, BCBM cells can also form direct synapses with neurons, tapping into excitatory input through glutamatergic receptors to drive tumor cell proliferation and survival. Concurrently, reprogrammed astrocytes establish gap junctions, secrete growth factors, and provide metabolic support. Together, tumor cells, neurons, and astrocytes form a pathological partnership locked in feedback loops sustaining metastatic progression. This review focuses on the unique mechanisms employed by distinct breast cancer subtypes and maps the metastatic progression from pre-metastatic to mature brain metastatic niche formation of BCBM. We highlight opportunities to repurpose neurological drugs to disrupt these communication axes.<\/jats:p>","DOI":"10.3390\/cells15080735","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:14Z","timestamp":1776854294000},"page":"735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neuroglial-Breast Cancer Crosstalk Shapes the Brain Metastatic Niche"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8071-2486","authenticated-orcid":false,"given":"Sabine","family":"Hombach-Klonisch","sequence":"first","affiliation":[{"name":"Departments of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Departments of Pathology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9656-1942","authenticated-orcid":false,"given":"Eric","family":"Hall","sequence":"additional","affiliation":[{"name":"Departments of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Amin","sequence":"additional","affiliation":[{"name":"Departments of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Fedora","sequence":"additional","affiliation":[{"name":"Departments of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry","family":"Vriend","sequence":"additional","affiliation":[{"name":"Departments of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall","family":"Pitz","sequence":"additional","affiliation":[{"name":"Departments of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"CancerCare MB, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0448-6741","authenticated-orcid":false,"given":"Thomas","family":"Klonisch","sequence":"additional","affiliation":[{"name":"Departments of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Departments of Pathology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"CancerCare MB, Winnipeg, MB R3E 0V9, Canada"},{"name":"Departments of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1093\/neuonc\/now127","article-title":"Updates in the management of brain metastases","volume":"18","author":"Arvold","year":"2016","journal-title":"Neuro Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/s41416-019-0619-y","article-title":"Impact of breast cancer molecular subtypes on the incidence, kinetics and prognosis of central nervous system metastases in a large multicentre real-life cohort","volume":"121","author":"Darlix","year":"2019","journal-title":"Br. 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