Mechanistically, GPNMB promotes tumor progression through: 1) RGD domain-mediated binding to α5β1 integrin, enhancing fibronectin adhesion and metastatic potential (Maric et al., 2015); 2) ADAM10-dependent ectodomain shedding, generating sGPNMB that stimulates angiogenesis via VEGF/NRP-1 signaling and endothelial cell migration; 3) direct interaction with FGFR1 in TNBC, activating PI3K-AKT pathway and enhancing sphere-forming capacity (Elhinnawi et al., 2024). The gene discussed is GPNMB; the disease is neoplasm.