title: Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Guilong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China. neuro_clk@hotmail.com.
authors.forename: Lukui
authors.initials: L
authors.lastname: Chen
authors.affiliation: Nanjing Zoonbio Biotechnology, Nanjing, 210014, China.
authors.forename: Kouhong
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, China.
authors.forename: Ahsan Ali
authors.initials: AA
authors.lastname: Khan
authors.affiliation: Cancer Research Center, Xiamen University, Xiamen, 361000, China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Nanjing Brain Hospital, Nanjing, 210029, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, 210029, China.
authors.forename: Ailin
authors.initials: A
authors.lastname: Lu
authors.affiliation: School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, China. guning@seu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D009361:Neoplasm Invasiveness; D039942:Neuropilin-1 / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C492009:GIPC1 protein, human; D034741:RNA, Small Interfering; D039942:Neuropilin-1
keywords: GIPC1; Gene therapy; Glioma; Neuropilin-1