Neuropilin-1 is a glial cell line-derived neurotrophic factor receptor in glioblastoma.
Neuropilin-1 is a glial cell line-derived neurotrophic factor receptor in glioblastoma.
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Neuropilin-1 是胶质母细胞瘤中胶质细胞系衍生的神经营养因子受体
DOI：
10.18632/oncotarget.18630
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发表时间：
2017-09-26
期刊：
影响因子：
--
通讯作者：
Gao DS
中科院分区：
文献类型：
--
作者：
Sun S;Lei Y;Li Q;Wu Y;Zhang L;Mu PP;Ji GQ;Tang CX;Wang YQ;Gao J;Gao J;Li L;Zhuo L;Li YQ;Gao DS
本研究的目的是确定胶质细胞源性神经营养因子（GDNF）在多形性胶质母细胞瘤（GBM）的受体。GST pull-down分析后，从C6大鼠胶质瘤细胞中纯化的膜蛋白进行液相色谱-串联质谱（LC-MS/MS）。利用Gene Ontology对差异表达的蛋白质进行了注释，神经纤毛蛋白-1（neuropilin-1，NRP 1）被鉴定为胶质瘤中GDNF的假定受体。NRP 1在人脑GBM和C6大鼠胶质瘤细胞中的表达高于正常人脑或原代大鼠星形胶质细胞。免疫荧光染色显示，NRP 1被GDNF募集到细胞膜上，并与GDNF共沉淀。使用NRP 1和GDNF蛋白结构在ZDOCK服务器中评估分子对接，并使用PyMOL分子图形系统进行可视化，揭示了NRP 1和GDNF之间的8个氢键和稳定的正负静电相互作用。RNAi敲除NRP 1可降低GDNF刺激的C6胶质瘤细胞的增殖。NRP 1是GBM患者生存和复发的独立危险因素。NRP 1 mRNA高表达与OS和DFS短相关（OS：χ2=4.6720，P=0.0307; DFS：χ2=11.013，P=0.0009）。因此，NRP 1是胶质瘤细胞中的GDNF受体和潜在的治疗靶点。
The aim of this study was to identify the receptor for glial cell line-derived neurotrophic factor (GDNF) in glioblastoma multiforme (GBM). After GST pull-down assays, membrane proteins purified from C6 rat glioma cells were subjected to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differentially expressed proteins were annotated using Gene Ontology, and neuropilin-1 (NRP1) was identified as the putative GDNF receptor in glioma. NRP1 was more highly expressed in human GBM brains and C6 rat glioma cells than in normal human brains or primary rat astrocytes. Immunofluorescence staining showed that NRP1 was recruited to the membrane by GDNF, and NRP1 co-immunoprecipitated with GDNF. Using the NRP1 and GDNF protein structures to assess molecular docking in the ZDOCK server and visualization with the PyMOL Molecular Graphics System revealed 8 H-bonds and stable positive and negative electrostatic interactions between NRP1 and GDNF. RNAi knockdown of NRP1 reduced proliferation of C6 glioma cells when stimulated with GDNF. NRP1 was an independent risk factor for both survival and recurrence in GBM patients. High NRP1 mRNA expression correlated with shorter OS and DFS (OS: χ2=4.6720, P=0.0307; DFS: χ2=11.013, P=0.0009). NRP1 is thus a GDNF receptor in glioma cells and a potential therapeutic target.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
8
作者：
Bagci, T.;Wu, J. K.;Jay, D. G.
通讯作者：
Jay, D. G.
影响因子：
2.8
作者：
Broholm, H;Laursen, H
通讯作者：
Laursen, H
靶向 Neuropilin-1 的单克隆抗体对胶质瘤细胞与纤连蛋白粘附的抑制作用
影响因子：
2.9
作者：
Chen, Lukui;Miao, Wei;Xu, Qiang
通讯作者：
Xu, Qiang
影响因子：
8.8
作者：
Goodman, Kerry M.;Kjaer, Svend;McDonald, Neil Q.
通讯作者：
McDonald, Neil Q.