Cancer Cell. 2008 Mar;13(3):235-48.

Yes and PI3K bind CD95 to signal invasion of glioblastoma.External

Kleber, S., Sancho-Martinez, I., Wiestler, B., Beisel, A., Gieffers, C., Hill, O., Thiemann, M., Mueller, W., Sykora, J., Kuhn, A., Schreglmann, N., Letellier, E., Zuliani, C., Klussmann, S., Teodorczyk, M., Grone, H. J., Ganten, T. M., Sultmann, H., Tuttenberg, J., von Deimling, A., Regnier-Vigouroux, A., Herold-Mende, C., Martin-Villalba, A.,
--- - Molecular Neurobiology Group, German Cancer Research Center (DKFZ), INF 581, 69120 Heidelberg, Germany.
Invasion 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-beta 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.
PMID: 18328427External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD FADD Link Fas Co-immunoprecipitation T98G 18328427
DD FADD Link Fas Co-immunoprecipitation LN-18 18328427
(Link: click this icon to show interactions only between the two corresponding DDs)