{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301558/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":[" Mus musculus","Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301558"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Brain FGF2 and NCAM1 contribute to FGFR1-dependent progression of ER+ breast cancer brain metastases in young and aged hosts [NanoString_DSP]","description":"Estrogen receptor positive (ER+) breast cancer (BC) represents a significant proportion of BC brain metastasis (BCBM) but remains understudied. Here, we report that FGFR1-amplification, a well-established driver of ER+ BC endocrine resistance, promotes ER+ BCBM colonization in young and aged mice, through brain-dependent mechanisms. FGFR1-dependent brain colonization in young and aged mice occurs via canonical FGF2/FGFR1 signaling and non-canonical NCAM1/FGFR1 interactions. Astrocytic FGF2-mediated paracrine activation of FGFR1 promoted BCBMs in estrogen36 treated young mice, but FGF2 signaling decreased in the brain with aging and estrogen-depletion. Neuronal and glial NCAM1, which remain unchanged in young and aged brains, promoted adhesion to neurons and migration of ER+ BC cells, suggesting that interactions with astrocytes and neurons facilitate early ER+ BCBM colonization through FGFR1. Importantly, FDA-approved FGFR inhibitors effectively blocked early but not late metastatic progression only in young mice, suggesting limited efficacy of FGFR inhibitors to block non-kinase-dependent FGFR1 functions in vivo.","dates":{"publication":"2026/05/06"},"accession":"GSE301558","cross_references":{"GSM":["GSM9085148","GSM9085149","GSM9085150","GSM9085153","GSM9085154","GSM9085151","GSM9085152","GSM9085157","GSM9085158","GSM9085155","GSM9085156","GSM9085139","GSM9085137","GSM9085138","GSM9085142","GSM9085143","GSM9085140","GSM9085141","GSM9085146","GSM9085147","GSM9085144","GSM9085145","GSM9085205","GSM9085206","GSM9085203","GSM9085204","GSM9085209","GSM9085207","GSM9085208","GSM9085171","GSM9085172","GSM9085170","GSM9085175","GSM9085176","GSM9085173","GSM9085174","GSM9085212","GSM9085179","GSM9085213","GSM9085177","GSM9085210","GSM9085211","GSM9085178","GSM9085159","GSM9085160","GSM9085161","GSM9085164","GSM9085165","GSM9085162","GSM9085163","GSM9085168","GSM9085201","GSM9085169","GSM9085202","GSM9085166","GSM9085200","GSM9085167","GSM9085227","GSM9085228","GSM9085225","GSM9085226","GSM9085229","GSM9085190","GSM9085193","GSM9085194","GSM9085191","GSM9085192","GSM9085197","GSM9085230","GSM9085231","GSM9085198","GSM9085195","GSM9085196","GSM9085234","GSM9085235","GSM9085232","GSM9085199","GSM9085233","GSM9085216","GSM9085217","GSM9085214","GSM9085215","GSM9085218","GSM9085219","GSM9085182","GSM9085183","GSM9085180","GSM9085181","GSM9085186","GSM9085220","GSM9085187","GSM9085184","GSM9085185","GSM9085223","GSM9085224","GSM9085188","GSM9085221","GSM9085189","GSM9085222","GSM9085132","GSM9085135","GSM9085136","GSM9085133","GSM9085134","GSM9085238","GSM9085239","GSM9085236","GSM9085237","GSM9085241","GSM9085242","GSM9085240","GSM9085245","GSM9085246","GSM9085243","GSM9085244"],"GPL":["34284","34290"],"GSE":["301558"],"taxon":[" Mus musculus","Homo sapiens"]}}