Fibroblast growth factor receptor 1 (FGFR1) and Integrin alpha-V beta-5 (αVβ5) (FGFR1 and αVβ5)

Fibroblast growth factor receptor 1 (FGFR1) and Integrin alpha-V beta-5 (αVβ5) are distinct cell surface receptors that frequently function as a coordinated co-receptor system in both viral pathogenesis and oncology. FGFR1 is a receptor tyrosine kinase that regulates essential cellular processes including proliferation, survival, and angiogenesis, while αVβ5 is an integrin heterodimer that mediates cell-matrix adhesion and clathrin-dependent endocytosis. Historically, these two proteins were identified as the primary co-receptors for Adeno-associated virus serotype 2 (AAV2), with FGFR1 facilitating viral attachment and αVβ5 promoting subsequent internalization. In the context of cancer, particularly glioblastoma and certain carcinomas, the co-expression and cross-talk between FGFR1 and αVβ5 contribute to tumor aggressiveness, invasion, and resistance to radiotherapy. Although they are currently targeted by separate classes of therapeutic agents—such as kinase inhibitors for FGFR1 and RGD-mimetic inhibitors for αVβ5—their functional synergy makes them a significant focus for combination therapy strategies aimed at overcoming treatment resistance.

Other names

FGFR1/αVβ5 co-receptor complexAAV2 co-receptorsFibroblast growth factor receptor 1Integrin alpha-V beta-5

FGFR1 inhibitors act as competitive antagonists of the ATP-binding site within the intracellular tyrosine kinase domain, preventing autophosphorylation and activation of downstream signaling pathways like RAS-MAPK. Integrin αVβ5 inhibitors, such as Cilengitide, are RGD-mimetic compounds that bind to the extracellular domain of the integrin, blocking its interaction with vitronectin and other matrix components to inhibit cell adhesion and FAK-mediated survival signaling.