Phosphoinositide Signaling and Angiogenesis

Cell-cell adherens junctions are mediated by the homophilic binding between single transmembrane protein cadherins (E-cadherin in epithelial cells and VE-cadherin in vescular endothelial cells). Despite VE-cadhetin function is important for development and cancer metastasis, little is known about how this protein functions and is regulated. My previous data demonstrated that PIPKIγ modulates epithelial cell morphology by directly binding to and regulating E-cadherin trafficking. PIPKIγ binds to VE-cadherin at a site which is highly conserved with the PIPKIγ binding region in E-cadherin, suggesting that PIPKIγ might also regulate VE-cadherin and participate in VEC functions. This is an intriguing possibility because if this were true, we would discover a protein that regulates both epithelial and endothelial cell migration through similar mechanisms. This could lead to development of drugs that may halt both EMT and neoangiogenesis. The findings that PIPKIγ associates with VE-cadherin suggest that this enzyme could be the critical regulator for the functions of VE-cadherin and for the organization of AJs. We will evaluate the role of PIPKIγ in modulating VE-cadherin and vascular functions. This will provide clues for future studies on neoangiogenesis.