GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301558/primaryOK200Other Mus musculusHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301558GEOGSEfalseBrain FGF2 and NCAM1 contribute to FGFR1-dependent progression of ER+ breast cancer brain metastases in young and aged hosts [NanoString_DSP]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.2026/05/06GSE301558GSM9085148GSM9085149GSM9085150GSM9085153GSM9085154GSM9085151GSM9085152GSM9085157GSM9085158GSM9085155GSM9085156GSM9085139GSM9085137GSM9085138GSM9085142GSM9085143GSM9085140GSM9085141GSM9085146GSM9085147GSM9085144GSM9085145GSM9085205GSM9085206GSM9085203GSM9085204GSM9085209GSM9085207GSM9085208GSM9085171GSM9085172GSM9085170GSM9085175GSM9085176GSM9085173GSM9085174GSM9085212GSM9085179GSM9085213GSM9085177GSM9085210GSM9085211GSM9085178GSM9085159GSM9085160GSM9085161GSM9085164GSM9085165GSM9085162GSM9085163GSM9085168GSM9085201GSM9085169GSM9085202GSM9085166GSM9085200GSM9085167GSM9085227GSM9085228GSM9085225GSM9085226GSM9085229GSM9085190GSM9085193GSM9085194GSM9085191GSM9085192GSM9085197GSM9085230GSM9085231GSM9085198GSM9085195GSM9085196GSM9085234GSM9085235GSM9085232GSM9085199GSM9085233GSM9085216GSM9085217GSM9085214GSM9085215GSM9085218GSM9085219GSM9085182GSM9085183GSM9085180GSM9085181GSM9085186GSM9085220GSM9085187GSM9085184GSM9085185GSM9085223GSM9085224GSM9085188GSM9085221GSM9085189GSM9085222GSM9085132GSM9085135GSM9085136GSM9085133GSM9085134GSM9085238GSM9085239GSM9085236GSM9085237GSM9085241GSM9085242GSM9085240GSM9085245GSM9085246GSM9085243GSM90852443428434290301558 Mus musculusHomo sapiens