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 J Liebl, Laurent Pelletier, François Berger, David Meyronet, Marie Castets, Patrick Mehlen

Research output: Contribution to journalArticle

5 Citations (Scopus)

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

Fingerprint

Ephrin-B3
EphA4 Receptor
Glioblastoma
Apoptosis
Growth
Ligands
Neoplasms
Cell Death
Ephrins
Lateral Ventricles
Receptor Protein-Tyrosine Kinases
Heterografts
Endothelial Cells
Biopsy

Keywords

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

ASJC Scopus subject areas

  • Oncology

Cite this

Royet, A., Broutier, L., Coissieux, M. M., Malleval, C., Gadot, N., Maillet, D., ... Mehlen, P. (2017). Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4. Oncotarget, 8(14), 23750-23759. https://doi.org/10.18632/oncotarget.16077

Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4. / Royet, Amélie; Broutier, Laura; Coissieux, Marie May; Malleval, Céline; Gadot, Nicolas; Maillet, Denis; Gratadou-Hupon, Lise; Bernet, Agnès; Nony, Pascale; Treilleux, Isabelle; Honnorat, Jérôme; Liebl, Daniel J; Pelletier, Laurent; Berger, François; Meyronet, David; Castets, Marie; Mehlen, Patrick.

In: Oncotarget, Vol. 8, No. 14, 2017, p. 23750-23759.

Research output: Contribution to journalArticle

Royet, A, Broutier, L, Coissieux, MM, Malleval, C, Gadot, N, Maillet, D, Gratadou-Hupon, L, Bernet, A, Nony, P, Treilleux, I, Honnorat, J, Liebl, DJ, Pelletier, L, Berger, F, Meyronet, D, Castets, M & Mehlen, P 2017, 'Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4', Oncotarget, vol. 8, no. 14, pp. 23750-23759. https://doi.org/10.18632/oncotarget.16077
Royet, Amélie ; Broutier, Laura ; Coissieux, Marie May ; Malleval, Céline ; Gadot, Nicolas ; Maillet, Denis ; Gratadou-Hupon, Lise ; Bernet, Agnès ; Nony, Pascale ; Treilleux, Isabelle ; Honnorat, Jérôme ; Liebl, Daniel J ; Pelletier, Laurent ; Berger, François ; Meyronet, David ; Castets, Marie ; Mehlen, Patrick. / Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4. In: Oncotarget. 2017 ; Vol. 8, No. 14. pp. 23750-23759.
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