PUBLICATION
Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4
- Authors
- Royet, A., Broutier, L., Coissieux, M.M., Malleval, C., Gadot, N., Maillet, D., Gratadou-Hupon, L., Bernet, A., Nony, P., Treilleux, I., Honnorat, J., Liebl, D., Pelletier, L., Berger, F., Meyronet, D., Castets, M., Mehlen, P.
- ID
- ZDB-PUB-171011-23
- Date
- 2017
- Source
- Oncotarget 8: 23750-23759 (Journal)
- Registered Authors
- Keywords
- Ephrin-B3/EphA4, angiogenesis, apoptosis, dependence receptors, glioblastoma
- MeSH Terms
-
- Animals
- Apoptosis/physiology
- Brain Neoplasms/genetics
- Brain Neoplasms/metabolism*
- Brain Neoplasms/pathology*
- Cell Line, Tumor
- Chick Embryo
- Ephrin-B3/metabolism*
- Female
- Glioblastoma/genetics
- Glioblastoma/metabolism*
- Glioblastoma/pathology*
- HEK293 Cells
- Human Umbilical Vein Endothelial Cells
- Humans
- Mice
- Mice, Nude
- Receptor, EphA4/metabolism*
- Zebrafish
- PubMed
- 28423606 Full text @ Oncotarget
Citation
Royet, A., Broutier, L., Coissieux, M.M., Malleval, C., Gadot, N., Maillet, D., Gratadou-Hupon, L., Bernet, A., Nony, P., Treilleux, I., Honnorat, J., Liebl, D., 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. 8:23750-23759.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping