机构：[a]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[b]The Experimental Center, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[c]Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[d]Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[e]Department of Neurology, University of Virginia, Charlottesville, VA, USA
Guanylate binding proteins (GBPs) are interferon-inducible large GTPases and play a crucial role in cell autonomous immunity. However, the biology function of GBPs in cancer remains elusive. GBP3 is specifically expressed in adult brain. Here we show that GBP3 is highly elevated in human glioma tumors and glioma cell lines. Overexpression of GBP3 dramatically increased glioma cell proliferation whereas silencing GBP3 by RNA interference produced opposite effects. We further showed that GBP3 expression was able to induce sequestosome-1(SQSTM1, also named p62) expression and activate extracellular signal-regulated kinase (ERK1/2). The SQSTM1-ERK1/2 signaling cascade was essential for GBP3-promoted cell growth because depletion of SQSTM1 markedly reduced the phosphorylated ERK1/2 levels and GBP3-mediated cell growth, and inhibition of mitogen-activated protein kinase/ERK kinase abolished GBP3-induced glioma cell proliferation. Consistently, GBP3 overexpression significantly promoted glioma tumor growth in vivo and its expression was inversely correlated with the survival rate of glioma patients. Taken together, these results for the first time suggest that GBP3 contributes to the proliferation of glioma cells via regulating SQSTM1-ERK1/2 pathway, and GBP3 might represent as a new potential therapeutic target against glioma. (C) 2017 Elsevier Inc. All rights reserved.
基金：
This study was supported by the National Natural Sciences Foundation
of China (81572480 to M.L), Program of Medical Innovation
Team and Leading Talent of Jiangsu Province (LJ201150), and Science
and Technology Plan Projects of Jiangsu Province (BL2012048).
M.L. is partially supported by Jiangsu Distinguished Medical Professorship
Award. This work was partially supported by the 2nd
Affiliated Hospital of Soochow University Preponderant Clinic
Discipline Group Project (XKQ2015004).
第一作者机构：[a]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[b]The Experimental Center, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
通讯作者：
通讯机构：[*1]Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[*2]Department of Neurology, University of Virginia, Charlottesville, VA, USA
推荐引用方式(GB/T 7714)：
Hui Xu,Lili Sun,Yanwen Zheng,et al.GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2018,495(1):446-453.doi:10.1016/j.bbrc.2017.11.050.
APA：
Hui Xu,Lili Sun,Yanwen Zheng,Shuye Yu,Jia Ou-yang...&Qing Lan.(2018).GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,495,(1)
MLA：
Hui Xu,et al."GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 495..1(2018):446-453
