{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPlexin‑B3 serves as a high‑affinity receptor for semaphorin 5A (Sema5A) that initiates diverse intracellular signaling cascades in multiple cell types—including fibroblasts, epithelial, endothelial, and neuronal cells—to regulate axon guidance and neurite outgrowth. In addition to its classical role in neural development, genetic studies have linked PLXNB3 to enhanced neurite extension, cognitive performance, and white matter development, while integrated computational analyses further support a conserved, co‑evolved interaction between PLXNB3 and Sema5A."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the central nervous system, a subpopulation of adult oligodendrocyte progenitor cells expresses plexin‑B3, and its upregulation is associated with increased secretion of amyloid‑β peptides. This relationship is underscored by the immunostaining of cortical senile plaques for plexin‑B3 in Alzheimer’s disease brains, suggesting that PLXNB3 may contribute to neurodegenerative pathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer, PLXNB3 exhibits context‑dependent functions. In glioma cells, activation by Sema5A via plexin‑B3 results in marked inhibition of cell migration and invasion through the modulation of Rho GTPase activity, cytoskeletal reorganization, and the promotion of astrocytic differentiation—processes involving key mediators such as protein kinase C and fascin‑1. In contrast, studies in triple‑negative breast cancer, hypoxic breast cancer, and pancreatic ductal adenocarcinoma demonstrate that elevated PLXNB3 expression can drive tumor proliferation, invasion, and metastasis by engaging MET/SRC, focal adhesion kinase signaling pathways, and promoting aerobic glycolysis. These findings collectively highlight PLXNB3 as an attractive target for therapeutic intervention across a spectrum of malignancies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stefania Artigiani, Paolo Conrotto, Pietro Fazzari, et al. 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