Focal adhesion kinase–Vascular endothelial growth factor receptor 3 protein–protein complex (FAK–VEGFR-3 complex)

The Focal adhesion kinase (FAK)–Vascular endothelial growth factor receptor 3 (VEGFR-3) protein–protein complex is a critical signaling assembly that plays a pivotal role in lymphangiogenesis and tumor progression (Garces et al., 2006). FAK, a non-receptor tyrosine kinase, physically associates with the C-terminal tail of VEGFR-3, a receptor tyrosine kinase primarily responsible for lymphatic vessel development (Kurenova et al., 2009). This interaction is essential for activating survival signaling pathways, such as PI3K/Akt, in both lymphatic endothelial cells and various cancer cell lines (Garces et al., 2006). In many malignancies, the overexpression of both FAK and VEGFR-3 correlates with increased lymph node metastasis and poor clinical prognosis (Schoenfeld et al., 2012). Therapeutic targeting of this complex involves the use of small molecules, like C4, which are designed to disrupt the specific protein-protein interface rather than the ATP-binding sites of the individual kinases (Kurenova et al., 2009). By inhibiting this interaction, these drugs can induce apoptosis in cancer cells and suppress the formation of tumor-associated lymphatic vessels, thereby limiting metastatic spread (Kurenova et al., 2009). This approach represents a targeted strategy to interfere with oncogenic signaling while potentially minimizing the off-target effects associated with traditional multi-kinase inhibitors.

Other names

FAK-VEGFR3 interactionPTK2-FLT4 complexFAK-VEGFR3 PPIFocal adhesion kinase-Vascular endothelial growth factor receptor 3 complex

Disruption of the physical protein-protein interaction between the focal adhesion kinase (FAK) scaffold and the vascular endothelial growth factor receptor 3 (VEGFR-3) C-terminal domain, thereby inhibiting downstream survival signaling pathways such as PI3K/Akt.