EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase.

Thumbnail Image



Journal Title

Journal ISSN

Volume Title

Repository Usage Stats


Citation Stats


Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumors in adults. Uncontrolled proliferation and abnormal cell migration are two prominent spatially and temporally disassociated characteristics of GBMs. In this study, we investigated the role of the receptor tyrosine kinase EphB2 in controlling the proliferation/migration dichotomy of GBM. We studied EphB2 gain of function and loss of function in glioblastoma-derived stem-like neurospheres, whose in vivo growth pattern closely replicates human GBM. EphB2 expression stimulated GBM neurosphere cell migration and invasion, and inhibited neurosphere cell proliferation in vitro. In parallel, EphB2 silencing increased tumor cell proliferation and decreased tumor cell migration. EphB2 was found to increase tumor cell invasion in vivo using an internally controlled dual-fluorescent xenograft model. Xenografts derived from EphB2-overexpressing GBM neurospheres also showed decreased cellular proliferation. The non-receptor tyrosine kinase focal adhesion kinase (FAK) was found to be co-associated with and highly activated by EphB2 expression, and FAK activation facilitated focal adhesion formation, cytoskeleton structure change and cell migration in EphB2-expressing GBM neurosphere cells. Taken together, our findings indicate that EphB2 has pro-invasive and anti-proliferative actions in GBM stem-like neurospheres mediated, in part, by interactions between EphB2 receptors and FAK. These novel findings suggest that tumor cell invasion can be therapeutically targeted by inhibiting EphB2 signaling, and that optimal antitumor responses to EphB2 targeting may require concurrent use of anti-proliferative agents.





Published Version (Please cite this version)


Publication Info

Wang, SD, P Rath, B Lal, J-P Richard, Y Li, CR Goodwin, J Laterra, S Xia, et al. (2012). EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase. Oncogene, 31(50). pp. 5132–5143. 10.1038/onc.2012.16 Retrieved from https://hdl.handle.net/10161/15822.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.



Courtney Rory Goodwin

Associate Professor of Neurosurgery

Associate Professor of Neurosurgery, Radiation Oncology, Orthopedic Surgery.
Director of Spine Oncology,
Associate Residency Program Director
Third Year Study Program Director Neurosciences, Duke University School of Medicine
Director of Spine Metastasis, Duke Center for Brain and Spine Metastasis, Department of Neurosurgery
Duke Cancer Institute, Duke University Medical Center

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.