SPARC mediates Src-induced disruption of actin cytoskeleton via inactivation of small GTPases Rho–Rac–Cdc42
作者： Praveen Bhoopathi , Christopher S. Gondi , Meena Gujrati , Dzung H. Dinh , Sajani S. Lakka
DOI: 10.1016/J.CELLSIG.2011.07.008
关键词:
摘要: The matricellular glycoprotein Secreted Protein Acidic and Rich in Cysteine (SPARC) plays an important role the regulation of cell adhesion proliferation as well tumorigenesis metastasis. Earlier, we reported that, addition to its potent anti-angiogenic functions, SPARC also induces apoptosis medulloblastoma cells, mediated by autophagy. We therefore sought investigate underlying molecular mechanism through which inhibits migration invasion Daoy both vitro vivo. For this study, used SPARC-overexpressing stable cells. overexpression cells inhibited vitro. Additionally, significantly suppressed activity Rho, Rac Cdc42, all regulate actin cytoskeleton. This suppression was accompanied increase phosphorylation Src at Tyr-416, led a loss stress fibers focal contacts decrease level cofilin. reduced cofilin, is indicative receding Rho function, turn inhibition active A. To confirm transfected parental with plasmid vector carrying siRNA against SPARC. Transfection reversed Src-mediated disruption cytoskeleton organization dephosphorylation cofilin activation Taken together, these results establish effector Src-induced subsequently decreased invasion.
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