机构：[1]The Experimental Center, the Second Affi liated Hospital of Soochow University, Suzhou, Jiangsu Province, China[2]Department of Neurosurgery, the Second Affi liated Hospital of Soochow University, Suzhou, Jiangsu Province, China[3]Department of Neurology, the Second Affi liated Hospital of Soochow University, Suzhou, Jiangsu Province, China[4]Department of Life Sciences, Luoyang Normal University, Luoyang, Henan Province, China[5]Department of Neurosurgery, the University of Tokyo, Bunkyo-ku, Tokyo, Japan[6]Department of Neurology, University of Virginia, Charlottesville, VA, USA
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.
基金：
This work was supported by the National Natural
Sciences Foundation of China (81172401 and 81572480,
to M.L.).
第一作者机构：[2]Department of Neurosurgery, the Second Affi liated Hospital of Soochow University, Suzhou, Jiangsu Province, China
共同第一作者：
通讯作者：
通讯机构：[1]The Experimental Center, the Second Affi liated Hospital of Soochow University, Suzhou, Jiangsu Province, China[2]Department of Neurosurgery, the Second Affi liated Hospital of Soochow University, Suzhou, Jiangsu Province, China[6]Department of Neurology, University of Virginia, Charlottesville, VA, USA
推荐引用方式(GB/T 7714)：
Qing Lan,Aidong Wang,Yanwei Cheng,et al.Guanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro[J].ONCOTARGET.2016,7(9):9680-91.doi:10.18632/oncotarget.7109.
APA：
Qing Lan,Aidong Wang,Yanwei Cheng,Akitaki Mukasa,Jiawei Ma...&Ming Li.(2016).Guanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro.ONCOTARGET,7,(9)
MLA：
Qing Lan,et al."Guanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro".ONCOTARGET 7..9(2016):9680-91
医学