Yes and PI3K bind CD95 to signal invasion of glioblastoma

Susanne Kleber; Ignacio Sancho-Martinez; Benedict Wiestler; Alexandra 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 Gröne; Tom M Ganten; Holger Sültmann; Jochen Tüttenberg; Andreas von Deimling; Anne Regnier-Vigouroux; Christel Herold-Mende; Ana Martin-Villalba

doi:10.1016/j.ccr.2008.02.003

Yes and PI3K bind CD95 to signal invasion of glioblastoma

Susanne Kleber, Ignacio Sancho-Martinez, Benedict Wiestler, Alexandra 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 Gröne, Tom M Ganten, Holger Sültmann, Jochen Tüttenberg, Andreas von DeimlingAnne Regnier-Vigouroux, Christel Herold-Mende, Ana Martin-Villalba

Centre for Stem Cells & Regenerative Medicine

Research output: Contribution to journal › Article › peer-review

266 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	235-248
Number of pages	14
Journal	CANCER CELL
Volume	13
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2008.02.003
Publication status	Published - 10 Mar 2008

Keywords

Animals
Antigens, CD95
Apoptosis
Brain Neoplasms
Cell Line, Tumor
Cell Movement
Death Domain Receptor Signaling Adaptor Proteins
Fas Ligand Protein
Glioblastoma
Glycogen Synthase Kinase 3
Humans
Matrix Metalloproteinases
Mice
Neoplasm Invasiveness
Neoplasm Transplantation
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-yes
RNA Interference
RNA, Small Interfering
Recombinant Fusion Proteins
Signal Transduction
Transfection
Transplantation, Isogeneic
Tumor Cells, Cultured
src-Family Kinases

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10.1016/j.ccr.2008.02.003

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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., Gröne, H.-J., Ganten, T. M., Sültmann, H., Tüttenberg, J., ... Martin-Villalba, A. (2008). Yes and PI3K bind CD95 to signal invasion of glioblastoma. CANCER CELL, 13(3), 235-248. https://doi.org/10.1016/j.ccr.2008.02.003

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title = "Yes and PI3K bind CD95 to signal invasion of glioblastoma",

abstract = "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.",

keywords = "Animals, Antigens, CD95, Apoptosis, Brain Neoplasms, Cell Line, Tumor, Cell Movement, Death Domain Receptor Signaling Adaptor Proteins, Fas Ligand Protein, Glioblastoma, Glycogen Synthase Kinase 3, Humans, Matrix Metalloproteinases, Mice, Neoplasm Invasiveness, Neoplasm Transplantation, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-yes, RNA Interference, RNA, Small Interfering, Recombinant Fusion Proteins, Signal Transduction, Transfection, Transplantation, Isogeneic, Tumor Cells, Cultured, src-Family Kinases",

author = "Susanne Kleber and Ignacio Sancho-Martinez and Benedict Wiestler and Alexandra Beisel and Christian Gieffers and Oliver Hill and Meinolf Thiemann and Wolf Mueller and Jaromir Sykora and Andreas Kuhn and Nina Schreglmann and Elisabeth Letellier and Cecilia Zuliani and Stefan Klussmann and Marcin Teodorczyk and Hermann-Josef Gr{\"o}ne and Ganten, {Tom M} and Holger S{\"u}ltmann and Jochen T{\"u}ttenberg and {von Deimling}, Andreas and Anne Regnier-Vigouroux and Christel Herold-Mende and Ana Martin-Villalba",

year = "2008",

month = mar,

day = "10",

doi = "10.1016/j.ccr.2008.02.003",

language = "English",

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journal = "CANCER CELL",

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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, Gröne, H-J, Ganten, TM, Sültmann, H, Tüttenberg, J, von Deimling, A, Regnier-Vigouroux, A, Herold-Mende, C & Martin-Villalba, A 2008, 'Yes and PI3K bind CD95 to signal invasion of glioblastoma', CANCER CELL, vol. 13, no. 3, pp. 235-248. https://doi.org/10.1016/j.ccr.2008.02.003

TY - JOUR

T1 - Yes and PI3K bind CD95 to signal invasion of glioblastoma

AU - Kleber, Susanne

AU - Sancho-Martinez, Ignacio

AU - Wiestler, Benedict

AU - Beisel, Alexandra

AU - Gieffers, Christian

AU - Hill, Oliver

AU - Thiemann, Meinolf

AU - Mueller, Wolf

AU - Sykora, Jaromir

AU - Kuhn, Andreas

AU - Schreglmann, Nina

AU - Letellier, Elisabeth

AU - Zuliani, Cecilia

AU - Klussmann, Stefan

AU - Teodorczyk, Marcin

AU - Gröne, Hermann-Josef

AU - Ganten, Tom M

AU - Sültmann, Holger

AU - Tüttenberg, Jochen

AU - von Deimling, Andreas

AU - Regnier-Vigouroux, Anne

AU - Herold-Mende, Christel

AU - Martin-Villalba, Ana

PY - 2008/3/10

Y1 - 2008/3/10

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD95

KW - Apoptosis

KW - Brain Neoplasms

KW - Cell Line, Tumor

KW - Cell Movement

KW - Death Domain Receptor Signaling Adaptor Proteins

KW - Fas Ligand Protein

KW - Glioblastoma

KW - Glycogen Synthase Kinase 3

KW - Humans

KW - Matrix Metalloproteinases

KW - Mice

KW - Neoplasm Invasiveness

KW - Neoplasm Transplantation

KW - Phosphatidylinositol 3-Kinases

KW - Proto-Oncogene Proteins c-yes

KW - RNA Interference

KW - RNA, Small Interfering

KW - Recombinant Fusion Proteins

KW - Signal Transduction

KW - Transfection

KW - Transplantation, Isogeneic

KW - Tumor Cells, Cultured

KW - src-Family Kinases

U2 - 10.1016/j.ccr.2008.02.003

DO - 10.1016/j.ccr.2008.02.003

M3 - Article

C2 - 18328427

SN - 1535-6108

VL - 13

SP - 235

EP - 248

JO - CANCER CELL

JF - CANCER CELL

IS - 3

ER -

Yes and PI3K bind CD95 to signal invasion of glioblastoma

Abstract

Keywords

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