Figure 2.

Schematic illustration of distinct signaling pathways induced by α2(IV)NC1. α2(IV)NC1 binds to αVβ3 and αVβ5 integrins on endothelial and tumor cells, and initiates two distinct signaling pathways. (1) Inhibition of phosphorylation of FAK/PI-3K/eIF4E/4E-BP1. (2) Activation of caspase-8 and -9 leading to activation of caspase-3. α2(IV)NC1 activates pro-caspase-8 and -9 directly through inhibition of FAK/PI3K/Akt/mTOR pathway. α2(IV)NC1 also indirectly enhances the mitochondrial pathway through Fas dependent caspase-8 activation, which results in inhibition of protein synthesis, DNA damage and cell death.