EphA3 Maintains Tumorigenicity and Is a Therapeutic Target in Glioblastoma Multiforme

Bryan W. Day; Brett W. Stringer; Fares Al-Ejeh; Michael J. Ting; John Wilson; Kathleen S. Ensbey; Paul R. Jamieson; Zara C. Bruce; Yi Chieh Lim; Carolin Offenhäuser; Sara Charmsaz; Leanne T. Cooper; Jennifer K. Ellacott; Angus Harding; Lucie Leveque; Po Inglis; Suzanne Allan; David G. Walker; Martin Lackmann; Geoffrey Osborne; Kum Kum Khanna; Brent A. Reynolds; Jason D. Lickliter; Andrew W. Boyd

doi:10.1016/j.ccr.2013.01.007

EphA3 Maintains Tumorigenicity and Is a Therapeutic Target in Glioblastoma Multiforme

Bryan W. Day^*, Brett W. Stringer, Fares Al-Ejeh, Michael J. Ting, John Wilson, Kathleen S. Ensbey, Paul R. Jamieson, Zara C. Bruce, Yi Chieh Lim, Carolin Offenhäuser, Sara Charmsaz, Leanne T. Cooper, Jennifer K. Ellacott, Angus Harding, Lucie Leveque, Po Inglis, Suzanne Allan, David G. Walker, Martin Lackmann, Geoffrey OsborneKum Kum Khanna, Brent A. Reynolds, Jason D. Lickliter, Andrew W. Boyd

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

181 Citations (Scopus)

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.

Original language	English
Pages (from-to)	238-248
Number of pages	11
Journal	Cancer Cell
Volume	23
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2013.01.007
Publication status	Published - 11 Feb 2013
Externally published	Yes

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Day, B. W., Stringer, B. W., Al-Ejeh, F., Ting, M. J., Wilson, J., Ensbey, K. S., Jamieson, P. R., Bruce, Z. C., Lim, Y. C., Offenhäuser, C., Charmsaz, S., Cooper, L. T., Ellacott, J. K., Harding, A., Leveque, L., Inglis, P., Allan, S., Walker, D. G., Lackmann, M., ... Boyd, A. W. (2013). EphA3 Maintains Tumorigenicity and Is a Therapeutic Target in Glioblastoma Multiforme. Cancer Cell, 23(2), 238-248. https://doi.org/10.1016/j.ccr.2013.01.007

@article{5cc13665cd884e69a39519d70a55fa31,

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.",

author = "Day, {Bryan W.} and Stringer, {Brett W.} and Fares Al-Ejeh and Ting, {Michael J.} and John Wilson and Ensbey, {Kathleen S.} and Jamieson, {Paul R.} and Bruce, {Zara C.} and Lim, {Yi Chieh} and Carolin Offenh{\"a}user and Sara Charmsaz and Cooper, {Leanne T.} and Ellacott, {Jennifer K.} and Angus Harding and Lucie Leveque and Po Inglis and Suzanne Allan and Walker, {David G.} and Martin Lackmann and Geoffrey Osborne and Khanna, {Kum Kum} and Reynolds, {Brent A.} and Lickliter, {Jason D.} and Boyd, {Andrew W.}",

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day = "11",

doi = "10.1016/j.ccr.2013.01.007",

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Day, BW, Stringer, BW, Al-Ejeh, F, Ting, MJ, Wilson, J, Ensbey, KS, Jamieson, PR, Bruce, ZC, Lim, YC, Offenhäuser, C, Charmsaz, S, Cooper, LT, Ellacott, JK, Harding, A, Leveque, L, Inglis, P, Allan, S, Walker, DG, Lackmann, M, Osborne, G, Khanna, KK, Reynolds, BA, Lickliter, JD & Boyd, AW 2013, 'EphA3 Maintains Tumorigenicity and Is a Therapeutic Target in Glioblastoma Multiforme', Cancer Cell, vol. 23, no. 2, pp. 238-248. https://doi.org/10.1016/j.ccr.2013.01.007

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AU - Day, Bryan W.

AU - Stringer, Brett W.

AU - Al-Ejeh, Fares

AU - Ting, Michael J.

AU - Wilson, John

AU - Ensbey, Kathleen S.

AU - Jamieson, Paul R.

AU - Bruce, Zara C.

AU - Lim, Yi Chieh

AU - Offenhäuser, Carolin

AU - Charmsaz, Sara

AU - Cooper, Leanne T.

AU - Ellacott, Jennifer K.

AU - Harding, Angus

AU - Leveque, Lucie

AU - Inglis, Po

AU - Allan, Suzanne

AU - Walker, David G.

AU - Lackmann, Martin

AU - Osborne, Geoffrey

AU - Khanna, Kum Kum

AU - Reynolds, Brent A.

AU - Lickliter, Jason D.

AU - Boyd, Andrew W.

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AB - 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.

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EphA3 Maintains Tumorigenicity and Is a Therapeutic Target in Glioblastoma Multiforme

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