Guanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro
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Qing Lan2,*, Aidong Wang1,*, Yanwei Cheng4, Akitaki Mukasa5, Jiawei Ma2, Lei Hong1, Shuye Yu1,3, Lili Sun1, Qiang Huang2, Benjamin Purow6, Ming Li1,2,6
1The Experimental Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
2Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
3Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
4Department of Life Sciences, Luoyang Normal University, Luoyang, Henan Province, China
5Department of Neurosurgery, the University of Tokyo, Bunkyo-ku, Tokyo, Japan
6Department of Neurology, University of Virginia, Charlottesville, VA, USA
*These authors have contributed equally to this work
Ming Li, e-mail: email@example.com
Keywords: GBP1, glioblastoma, EGFRvIII, tumor growth, survival
Received: April 15, 2015 Accepted: January 22, 2016 Published: February 01, 2016
Glioblastoma multiforme (GBM) is the most common and deadly primary brain tumor in adults. Epidermal growth factor receptor (EGFR) is frequently amplified and mutated in GBM. We previously reported that Guanylate binding protein-1 (GBP1) is a novel transcriptional target gene of EGFR and plays a role in GBM invasion. Here we demonstrate that GBP1 can also be induced by EGFRvIII at the transcriptional level through the p38 MAPK/Yin Yang 1 (YY1) signaling pathway. Silencing of GBP1 by RNA interference significantly inhibits EGFRvIII-mediated GBM cell proliferation in vitro and in a mouse model. Overexpression of GBP1 has no obvious effect on glioblastoma cell proliferation in vitro. In contrast, in an orthotopic glioma mouse model GBP1 overexpression significantly promotes glioma growth and reduces survival rate of glioma-bearing mice by increasing cell proliferation and decreasing cell apoptosis in tumor. Clinically, GBP1 expression is elevated in human GBM tumors and positively correlates with EGFRvIII status in GBM specimens, and its expression is inversely correlated with the survival rate of GBM patients. Taken together, these results reveal that GBP1 may serve as a potential therapeutic target for GBMs with EGFRvIII mutation.
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