Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression.
Guilong Zhang, Lukui Chen, Kouhong Sun, Ahsan Ali Khan, Jianghua Yan, Hongyi Liu, Ailin Lu, Ning Gu
Author Information
Guilong Zhang: Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Lukui Chen: Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China. neuro_clk@hotmail.com.
Kouhong Sun: Nanjing Zoonbio Biotechnology, Nanjing, 210014, China.
Ahsan Ali Khan: Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
Jianghua Yan: Cancer Research Center, Xiamen University, Xiamen, 361000, China.
Hongyi Liu: Department of Neurosurgery, Nanjing Brain Hospital, Nanjing, 210029, China.
Ailin Lu: Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, 210029, China.
Ning Gu: School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, China. guning@seu.edu.cn.
中文译文
English
Glioma occurs due to multi-gene abnormalities. Neuropilin-1 (NRP-1), as a transmembrane protein, involves in Glioma proliferation, invasion, and migration, as well as tumor angiogenesis. The cytoplasmic protein, GAIP/RGS19-interacting protein (GIPC1), could regulate the clathrin-vesicles trafficking and recycling. Here, we show that NRP-1 co-localizes and co-immunoprecipitates with GIPC1, and the C-terminal SEA-COOH motif of NRP-1 interacts specially with the named from three proteins: PSD-95 (a 95 kDa protein involved in signaling at the post-synaptic density), DLG (the Drosophila melanogaster Discs Large protein ) and ZO-1 (the zonula occludens 1 protein involved in maintenance of epithelial polarity) (PDZ) domain of GIPC1 in Glioma cells. Knockdown of GIPC1 by small interfering RNA (siRNA) significantly reduces the proliferation and invasion of Glioma cells in vitro and increases its apoptosis. Furthermore, si-GIPC1 prevents the action of adaptor proteins adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1 (APPL1) and p130Cas and inhibits the downstream kirsten rat sarcoma viral oncogene homolog (KRAS)-ERK signaling pathway. This study demonstrated that NRP-1/GIPC1 pathway plays a vital role in Glioma progression, and it is a potential important target for multi-gene combined therapeutics.
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Adaptor Proteins, Signal Transducing
Animals
Apoptosis
Biomarkers, Tumor
Blotting, Western
Cell Movement
Cell Proliferation
Disease Progression
Flow Cytometry
Fluorescent Antibody Technique
Glioma
Humans
Immunoenzyme Techniques
Immunoprecipitation
Neoplasm Invasiveness
Neuropilin-1
Protein Binding
RNA, Small Interfering
Rats
Signal Transduction
Tumor Cells, Cultured
Adaptor Proteins, Signal Transducing
Biomarkers, Tumor
GIPC1 protein, human
RNA, Small Interfering
Neuropilin-1