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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; Pelletier, Laurent; Berger, François; Meyronet, David; Castets, Marie; Mehlen, Patrick.
Afiliação
  • Royet A; Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
  • Broutier L; Netris Pharma, 69008 Lyon, France.
  • Coissieux MM; Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
  • Malleval C; Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
  • Gadot N; Lyon Neurosciences Research Center, Neuro-Oncology and Neuro-Inflammation laboratory, INSERM UMR1028, CNRS UMR5292, Université de Lyon, 69372 Lyon Cedex 08, France.
  • Maillet D; Research Pathology, Department of Translational Research and Innovation, Centre Léon Bérard, 69008 Lyon, France.
  • Gratadou-Hupon L; Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
  • Bernet A; Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
  • Nony P; Netris Pharma, 69008 Lyon, France.
  • Treilleux I; Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
  • Honnorat J; Netris Pharma, 69008 Lyon, France.
  • Liebl D; Netris Pharma, 69008 Lyon, France.
  • Pelletier L; Research Pathology, Department of Translational Research and Innovation, Centre Léon Bérard, 69008 Lyon, France.
  • Berger F; Lyon Neurosciences Research Center, Neuro-Oncology and Neuro-Inflammation laboratory, INSERM UMR1028, CNRS UMR5292, Université de Lyon, 69372 Lyon Cedex 08, France.
  • Meyronet D; University of Miami Miller School of Medicine, The Miami Project to Cure Paralysis, Miami, Fl 33136, USA.
  • Castets M; Grenoble Institut des Neurosciences, Nanomedicine and Brain Laboratory, INSERM U 836, BP 170, F38042 Grenoble Cedex 9, France.
  • Mehlen P; Grenoble Institut des Neurosciences, Nanomedicine and Brain Laboratory, INSERM U 836, BP 170, F38042 Grenoble Cedex 9, France.
Oncotarget ; 8(14): 23750-23759, 2017 Apr 04.
Article em En | MEDLINE | ID: mdl-28423606
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Receptor EphA4 / Efrina-B3 Limite: Animals / Female / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2017 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Glioblastoma / Receptor EphA4 / Efrina-B3 Limite: Animals / Female / Humans Idioma: En Revista: Oncotarget Ano de publicação: 2017 Tipo de documento: Article País de afiliação: França