The long-term objective of our research is to develop specific inhibitors of Crk and CrkL for glioblastoma (GBM) treatment. As an important step toward developing a novel therapy for GBM, this project aimed at obtaining key in vitro data to address the feasibility of Crk and CrkL as therapeutic targets. In the proposed research, human GBM cell lines were used to test whether Crk and CrkL are required for GBM cell growth and migration.
We compared commercially available small interfering RNAs (siRNAs) to identify specific and potent suppressors of Crk and CrkL expression using a human glioblastoma cell line. Using these siRNAs, we induced single and double knockdowns of Crk and CrkL in a glioblastoma cell line to analyze quantitatively the resulting cellular phenotypes. Our findings elaborate the predominant role of CrkL and the essential overlapping functions of Crk and CrkL in glioblastoma cell structure, growth, adhesion, migration, and invasion. Our study indicates that cell migration is a specific, measurable, cellular outcome that requires both Crk and CrkL, thus providing a pathway for translational exploration.