Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4

Amélie Royet, Laura Broutier, Marie May Coissieux, Céline Malleval, Nicolas Gadot, Denis Maillet, Lise Gratadou-Hupon, Agnès Bernet, Pascale Nony, Isabelle Treilleux, Jérôme Honnorat, Daniel Liebl, Laurent Pelletier, François Berger, David Meyronet, Marie Castets, Patrick Mehlen

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)23750-23759
Number of pages10
JournalOncotarget
Volume8
Issue number14
DOIs
StatePublished - 2017

Keywords

  • Angiogenesis
  • Apoptosis
  • Dependence receptors
  • Ephrin-B3/EphA4
  • Glioblastoma

ASJC Scopus subject areas

  • Oncology

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