In the proposed research, effective gene knockdown of p130Cas (BCAR1) has been established, and comparison between Crk/CrkL knockdown and p130Cas (BCAR1) knockdown provided insights into p130Cas-dependent functions of Crk/CrkL. Combined knockdown revealed that Crk, CrkL, and p130Cas are important for GBM cell adhesion, migration, and invasion.
A variety of phosphorylated p130Cas-mimicking peptides were designed, synthesized, and tested for their inhibitory effects on the Crk/CrkL-p130Cas interaction. While a dimer peptide exhibited the highest inhibitory effect, a cyclized dimer peptide was delivered into GBM cells with the highest efficiency. The results demonstrate that phosphorylated p130Cas-mimicking peptides can be developed as inhibitors of Crk, CrkL, and p130Cas proteins.