title: EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme.
abstract: Significant endeavor has been applied to identify functional therapeutic targets in glioblastoma (GBM) to halt the growth of this aggressive cancer. We show that the receptor tyrosine kinase EphA3 is frequently overexpressed in GBM and, in particular, in the most aggressive mesenchymal subtype. Importantly, EphA3 is highly expressed on the tumor-initiating cell population in glioma and appears critically involved in maintaining tumor cells in a less differentiated state by modulating mitogen-activated protein kinase signaling. EphA3 knockdown or depletion of EphA3-positive tumor cells reduced tumorigenic potential to a degree comparable to treatment with a therapeutic radiolabelled EphA3-specific monoclonal antibody. These results identify EphA3 as a functional, targetable receptor in GBM.
authors: Brain Cancer Research Unit and Leukaemia Foundation Research Unit, Queensland Institute of Medical Research, Brisbane 4006, Australia. bryan.day@qimr.edu.au
authors: Bryan W
authors: BW
authors: Day
authors: Brett W
authors: BW
authors: Stringer
authors: Fares
authors: F
authors: Al-Ejeh
authors: Michael J
authors: MJ
authors: Ting
authors: John
authors: J
authors: Wilson
authors: Kathleen S
authors: KS
authors: Ensbey
authors: Paul R
authors: PR
authors: Jamieson
authors: Zara C
authors: ZC
authors: Bruce
authors: Yi Chieh
authors: YC
authors: Lim
authors: Carolin
authors: C
authors: Offenhäuser
authors: Sara
authors: S
authors: Charmsaz
authors: Leanne T
authors: LT
authors: Cooper
authors: Jennifer K
authors: JK
authors: Ellacott
authors: Angus
authors: A
authors: Harding
authors: Lucie
authors: L
authors: Leveque
authors: Po
authors: P
authors: Inglis
authors: Suzanne
authors: S
authors: Allan
authors: David G
authors: DG
authors: Walker
authors: Martin
authors: M
authors: Lackmann
authors: Geoffrey
authors: G
authors: Osborne
authors: Kum Kum
authors: KK
authors: Khanna
authors: Brent A
authors: BA
authors: Reynolds
authors: Jason D
authors: JD
authors: Lickliter
authors: Andrew W
authors: AW
authors: Boyd
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D036121:Receptor, EphA3; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D034741:RNA, Small Interfering; C491718:EPHA3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036121:Receptor, EphA3; D020928:Mitogen-Activated Protein Kinases