c-Cbl regulates glioma invasion through matrix metalloproteinase 2.

c-Cbl, a multifunctional adaptor and an E3 ubiquitin ligase, plays a role in such cytoskeleton-mediated events as cell adhesion and migration. Invasiveness of human glioma is dependent on cell adhesion, migration, and degradation of extracellular matrix (ECM). However, the function of c-Cbl in glioma invasion has never been investigated. We report here, for the first time, that c-Cbl plays a positive role in the invasion of ECM by SNB19 glioma cells. RNAi-mediated depletion of c-Cbl decreases SNB19 cell invasion and expression of matrix metalloproteinase 2 (MMP2). Consistent with these findings, SNB19 cells expressing wild-type, but not mutant c-Cbl show increased invasion and MMP2 expression. We demonstrate that the observed role of c-Cbl in invasion of SNB19 cells is not mediated by the previously shown effects of c-Cbl on cell adhesion and migration or on EGFR signaling. Together, our results suggest that c-Cbl promotes glioma invasion through up-regulation of MMP2.