Open AccessGuanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro
Author(s) -
Qing Lan,
Aidong Wang,
Yanwei Cheng,
Akitaki Mukasa,
Jiawei Ma,
Lei Hong,
Shuye Yu,
Lili Sun,
Qiang Huang,
Benjamin Purow,
Ming Li
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.7109
Subject(s) - cancer research , glioma , gene silencing , epidermal growth factor receptor , cell growth , biology , apoptosis , rna interference , small hairpin rna , microbiology and biotechnology , cancer , gene , gene knockdown , rna , genetics , biochemistry
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.