title: Guanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro.
abstract: 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.
authors: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors: Qing
authors: Q
authors: Lan
authors: The Experimental Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors: Aidong
authors: A
authors: Wang
authors: Department of Life Sciences, Luoyang Normal University, Luoyang, Henan Province, China.
authors: Yanwei
authors: Y
authors: Cheng
authors: Department of Neurosurgery, the University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Akitaki
authors: A
authors: Mukasa
authors: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors: Jiawei
authors: J
authors: Ma
authors: The Experimental Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors: Lei
authors: L
authors: Hong
authors: The Experimental Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.|Department of Neurology, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors: Shuye
authors: S
authors: Yu
authors: The Experimental Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors: Lili
authors: L
authors: Sun
authors: Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.
authors: Qiang
authors: Q
authors: Huang
authors: Department of Neurology, University of Virginia, Charlottesville, VA, USA.
authors: Benjamin
authors: B
authors: Purow
authors: The Experimental Center, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.|Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China.|Department of Neurology, University of Virginia, Charlottesville, VA, USA.
authors: Ming
authors: M
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014183:Transplantation, Heterologous; D050986:YY1 Transcription Factor / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C490287:GBP1 protein, human; D034741:RNA, Small Interfering; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins
keywords: EGFRvIII; GBP1; glioblastoma; survival; tumor growth