Yes and PI3K Bind CD95 to Signal Invasion of Glioblastoma

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• 作者：Susanne Kleber ; Ignacio Sancho-Martinez ; Benedict Wiestler ; Alex ; ra Beisel ; Christian Gieffers ; Oliver Hill ; Meinolf Thiemann ; Wolf Mueller ; Jaromir Sykora ; Andreas Kuhn ; Nina Schreglmann ; Elisabeth Letellier ; Cecilia Zuliani ; Stefan Klussmann ; Marcin Teodorczyk ; Hermann-Josef Grö ; ne ; Tom M. Gan
• 刊名：Cancer Cell
• 出版年：2008
• 出版时间：11 March 2008
• 年：2008
• 卷：13
• 期：3
• 页码：235-248
• 全文大小：1896 K

文摘

Summary

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-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.