Figure 2.

Model for cooperation of VE-cadherin and EphA2 during vascular mimicry of melanoma cells. Hypothetical model for the regulation of EphA2 by VE-cadherin in aggressive melanoma cells. In this model, VE-cadherin association with other VE-cadherin molecules on adjacent cells facilitates the organization of EphA2, either by interacting directly or indirectly with EphA2, on the cell membrane. Once organized on the cell membrane, EphA2 is able to bind to its ligand, ephrin-A1, resulting in the phosphorylation of the receptor. Phosphorylated EphA2 can then bind to PI 3-kinase and lead to its activation. Furthermore, phosphorylated EphA2 can bind to phosphorylated FAK. The ability of EphA2 to interact with both FAK and PI 3-kinase may play an important role in the signaling pathways underlying melanoma cell vasculogenic mimicry. (Developed by A. Hess)