Open AccessEphrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4
Author(s) -
Amélie Royet,
Laura Broutier,
Marie–May Coissieux,
Céline Malleval,
Nicolas Gadot,
Denis Maillet,
Lise Gratadou-Hupon,
Agnès Bernet,
Pascale y,
Isabelle Treilleux,
Jérôme Honnorat,
Daniel J. Liebl,
Laurent Pelletier,
François Berger,
David Meyronet,
Marie Castets,
Patrick Mehlen
Publication year - 2017
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.16077
Subject(s) - ephrin , cancer research , angiogenesis , receptor tyrosine kinase , erythropoietin producing hepatocellular (eph) receptor , apoptosis , gene silencing , receptor , programmed cell death , biology , microbiology and biotechnology , medicine , signal transduction , genetics , gene
EphA4, an Ephrins tyrosine kinase receptor, behaves as a dependence receptor (DR) by triggering cell apoptosis in the absence of its ligand Ephrin-B3. DRs act as conditional tumor suppressors, engaging cell death based on ligand availability; this mechanism is bypassed by overexpression of DRs ligands in some aggressive cancers. The pair EphA4/Ephrin-B3 favors survival of neuronal progenitors of the brain subventricular zone, an area where glioblastoma multiform (GBM) are thought to originate. Here, we report that Ephrin-B3 is highly expressed in human biopsies and that it inhibits EphA4 pro-apoptotic activity in tumor cells. Angiogenesis is directly correlated with GBM aggressiveness and we demonstrate that Ephrin-B3 also supports the survival of endothelial cells in vitro and in vivo. Lastly, silencing of Ephrin-B3 decreases tumor vascularization and growth in a xenograft mice model. Interference with EphA4/Ephrin-B3 interaction could then be envisaged as a relevant strategy to slow GBM growth by enhancing EphA4-induced cell death.