Author/Authors :
Kleber، نويسنده , , Susanne and Sancho-Martinez، نويسنده , , Ignacio and Wiestler، نويسنده , , Benedict and Beisel، نويسنده , , Alexandra and Gieffers، نويسنده , , Christian and Hill، نويسنده , , Oliver and Thiemann، نويسنده , , Meinolf and Mueller، نويسنده , , Wolf and Sykora، نويسنده , , Jaromir and Kuhn، نويسنده , , Andreas and Schreglmann، نويسنده , , Nina and Letellier، نويسنده , , Elisabeth and Zuliani، نويسنده , , Cecilia and Klussmann، نويسنده , , Stefan and Teodorczyk، نويسنده , , Marcin and Grِne، نويسنده , , Hermann-Josef and Ganten، نويسنده , , Tom M. and Sültmann، نويسنده , , Holger and Tüttenberg، نويسنده , , Jochen and von Deimling، نويسنده , , Andreas and Regnier-Vigouroux، نويسنده , , Anne and Herold-Mende، نويسنده , , Christel and Martin-Villalba، نويسنده , , Ana، نويسنده ,
Abstract :
Summary
on of surrounding brain tissue by isolated tumor cells represents one of the main obstacles to a curative therapy of glioblastoma multiforme. Here we unravel a mechanism regulating glioma infiltration. Tumor interaction with the surrounding brain tissue induces CD95 Ligand expression. Binding of CD95 Ligand to CD95 on glioblastoma cells recruits the Src family member Yes and the p85 subunit of phosphatidylinositol 3-kinase to CD95, which signal invasion via the glycogen synthase kinase 3-β pathway and subsequent expression of matrix metalloproteinases. In a murine syngeneic model of intracranial GBM, neutralization of CD95 activity dramatically reduced the number of invading cells. Our results uncover CD95 as an activator of PI3K and, most importantly, as a crucial trigger of basal invasion of glioblastoma in vivo.
