Guanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro

被引:25
作者
Lan, Qing [2 ]
Wang, Aidong [1 ]
Cheng, Yanwei [4 ]
Mukasa, Akitaki [5 ]
Ma, Jiawei [2 ]
Hong, Lei [1 ]
Yu, Shuye [1 ,3 ]
Sun, Lili [1 ]
Huang, Qiang [2 ]
Purow, Benjamin [6 ]
Li, Ming [1 ,2 ,6 ]
机构
[1] Soochow Univ, Affiliated Hosp 2, Expt Ctr, Suzhou, Jiangsu, Peoples R China
[2] Soochow Univ, Affiliated Hosp 2, Dept Neurosurg, Suzhou, Jiangsu, Peoples R China
[3] Soochow Univ, Affiliated Hosp 2, Dept Neurol, Suzhou, Jiangsu, Peoples R China
[4] Luoyang Normal Univ, Dept Life Sci, Luoyang, Henan Province, Peoples R China
[5] Univ Tokyo, Dept Neurosurg, Bunkyo Ku, Tokyo 113, Japan
[6] Univ Virginia, Dept Neurol, Charlottesville, VA USA
关键词
GBP1; glioblastoma; EGFRvIII; tumor growth; survival; FACTOR RECEPTOR COMMON; NUCLEOTIDE-BINDING; SIGNALING NETWORKS; TUMOR; ACTIVATION; PHENOTYPE; INVASION; GLIOMA;
D O I
10.18632/oncotarget.7109
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:9680 / 9691
页数:12
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