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. J. Cell. Biochem. 111: 1169–1178, 2010. © 2010 Wiley‐Liss, Inc.     

Matrix metalloproteinase 2 promotes cell growth and invasion in colorectal cancer

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the western world. In this study, we evaluated the expression of matrix metalloproteinase 2 gene (MMP2) in CRC and analyzed its correlation with clinicopathological features. We found that the expression of MMP2 was significantly higher in CRC tissues than in the colorectal tissues. In addition, high levels of MMP2 protein were positively correlated with the status of tumor size, lymph node metastasis, distant metastasis, Dukes' stage, and tumor invasion. Moreover, patients with higher MMP2 levels had markedly shorter overall survivals than those with low MMP2 levels. Multivariate analysis results suggested that the level of MMP2 expression is an independent prognostic indicator for the survival of patients with CRC. Silencing MMP2 expression in CRC cell lines with lentiviral-mediated shRNA markedly suppressed cell proliferation, colony formation, and invasion. Furthermore, we observed that vascular endothelial growth factor (VEGF) and membrane type 1 (MT1)-MMP protein levels were decreased in MMP2-down-regulated colorectal cells. Therefore, our study demonstrated that MMP2 is an important factor related to carcinogenesis and metastasis of CRC, and MMP2 promotes CRC cell growth and invasion by up-regulating VEGF and MT1-MMP expression, which makes this pathway a potential target for cancer treatment.