EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme

Bryan 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 Offenhauser, Sara Charmsaz, Leanne T Cooper, Jennifer K Ellacott, Angus Harding, Lucie Leveque, Po L Inglis, Suzanne Allan, David G Walker, Martin Lackmann, Geoffrey W OsborneKum Kum Khanna, Brent A Reynolds, Jason D Lickliter, Andrew W Boyd

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111 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 languageEnglish
Pages (from-to)238 - 248
Number of pages11
JournalCancer Cell
Volume23
Issue number2
DOIs
Publication statusPublished - 2013

Cite this

Day, B., Stringer, B. W., Al-Ejeh, F., Ting, M. J., Wilson, J., Ensbey, K. S., ... 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
Day, Bryan ; Stringer, Brett W ; Al-Ejeh, Fares ; Ting, Michael J ; Wilson, John ; Ensbey, Kathleen S ; Jamieson, Paul R ; Bruce, Zara C ; Lim, Yi Chieh ; Offenhauser, Carolin ; Charmsaz, Sara ; Cooper, Leanne T ; Ellacott, Jennifer K ; Harding, Angus ; Leveque, Lucie ; Inglis, Po L ; Allan, Suzanne ; Walker, David G ; Lackmann, Martin ; Osborne, Geoffrey W ; Khanna, Kum Kum ; Reynolds, Brent A ; Lickliter, Jason D ; Boyd, Andrew W. / EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme. In: Cancer Cell. 2013 ; Vol. 23, No. 2. pp. 238 - 248.
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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.",
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Day, B, Stringer, BW, Al-Ejeh, F, Ting, MJ, Wilson, J, Ensbey, KS, Jamieson, PR, Bruce, ZC, Lim, YC, Offenhauser, C, Charmsaz, S, Cooper, LT, Ellacott, JK, Harding, A, Leveque, L, Inglis, PL, Allan, S, Walker, DG, Lackmann, M, Osborne, GW, 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

EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme. / Day, Bryan; Stringer, Brett W; Al-Ejeh, Fares; Ting, Michael J; Wilson, John; Ensbey, Kathleen S; Jamieson, Paul R; Bruce, Zara C; Lim, Yi Chieh; Offenhauser, Carolin; Charmsaz, Sara; Cooper, Leanne T; Ellacott, Jennifer K; Harding, Angus; Leveque, Lucie; Inglis, Po L; Allan, Suzanne; Walker, David G; Lackmann, Martin; Osborne, Geoffrey W; Khanna, Kum Kum; Reynolds, Brent A; Lickliter, Jason D; Boyd, Andrew W.

In: Cancer Cell, Vol. 23, No. 2, 2013, p. 238 - 248.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - EphA3 maintains tumorigenicity and is a therapeutic target in glioblastoma multiforme

AU - Day, Bryan

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 - Offenhauser, Carolin

AU - Charmsaz, Sara

AU - Cooper, Leanne T

AU - Ellacott, Jennifer K

AU - Harding, Angus

AU - Leveque, Lucie

AU - Inglis, Po L

AU - Allan, Suzanne

AU - Walker, David G

AU - Lackmann, Martin

AU - Osborne, Geoffrey W

AU - Khanna, Kum Kum

AU - Reynolds, Brent A

AU - Lickliter, Jason D

AU - Boyd, Andrew W

PY - 2013

Y1 - 2013

N2 - 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.

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.

UR - http://goo.gl/6UKzjZ

U2 - 10.1016/j.ccr.2013.01.007

DO - 10.1016/j.ccr.2013.01.007

M3 - Article

VL - 23

SP - 238

EP - 248

JO - Cancer Cell

JF - Cancer Cell

SN - 1535-6108

IS - 2

ER -