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c‐Cbl regulates glioma invasion through matrix metalloproteinase 2
Authors:Hojin Lee  Alexander Y Tsygankov
Institution:1. Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania;2. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania;3. Sol Sherry Thrombosis Center, Temple University School of Medicine, Philadelphia, PA
Abstract: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.
Keywords:c‐Cbl  glioma  invasion  MMP2
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