Basic fibroblast growth factor–Fibroblast growth factor receptor 1 interaction (bFGF–FGFR1)

The interaction between Basic Fibroblast Growth Factor (bFGF, also known as FGF2) and Fibroblast Growth Factor Receptor 1 (FGFR1) is a critical signaling axis involved in various physiological and pathological processes (UniProt P09038, P11362). bFGF binds to the extracellular domain of FGFR1, a process facilitated by heparan sulfate proteoglycans, leading to receptor dimerization and autophosphorylation of the intracellular tyrosine kinase domain (PubMed: 25135934). This activation triggers downstream signaling cascades, including the RAS-MAPK, PI3K-AKT, and PLCγ pathways, which promote cell survival, proliferation, and migration. In oncology, dysregulation of this interaction through FGFR1 amplification or FGF2 overexpression is frequently observed in squamous cell lung cancer, breast cancer, and other solid tumors, driving tumor growth and neoangiogenesis (PubMed: 31110039). Consequently, this interaction is a major therapeutic target, with several small-molecule tyrosine kinase inhibitors (TKIs) like Erdafitinib and Pemigatinib approved to block FGFR signaling (FDA). Beyond cancer, the bFGF–FGFR1 axis plays roles in wound healing and cardiovascular repair, though systemic inhibition can lead to specific toxicities such as hyperphosphatemia due to the disruption of phosphate homeostasis regulated by the FGF23-FGFR1-Klotho axis.

Other names

FGF2–FGFR1 interactionFibroblast growth factor 2–Fibroblast growth factor receptor 1 complexHeparin-binding growth factor 2–FGFR1 interactionbFGF–FGFR1 signaling axis

Inhibition of the receptor tyrosine kinase activity or blocking the binding of the bFGF ligand to the FGFR1 receptor to prevent downstream signaling pathways such as MAPK/ERK, PI3K/AKT, and PLCγ.