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Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression

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Tumor Biology

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.

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Acknowledgments

Our study has been kindly supported by the National Natural Science Foundation of China (No. 81471780).

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Authors and Affiliations

  1. Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nan**g, 210009, China

    Guilong Zhang, Lukui Chen & Ahsan Ali Khan

  2. Nan**g Zoonbio Biotechnology, Nan**g, 210014, China

    Kouhong Sun

  3. Cancer Research Center, **amen University, **amen, 361000, China

    Jianghua Yan

  4. Department of Neurosurgery, Nan**g Brain Hospital, Nan**g, 210029, China

    Hongyi Liu

  5. Department of Neurosurgery, Jiangsu Province Hospital, Nan**g, 210029, China

    Ailin Lu

  6. School of Biological Science and Medical Engineering, Southeast University, Nan**g, 210009, China

    Ning Gu

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  1. Guilong Zhang
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Zhang, G., Chen, L., Sun, K. et al. Neuropilin-1 (NRP-1)/GIPC1 pathway mediates glioma progression. Tumor Biol. 37, 13777–13788 (2016). https://doi.org/10.1007/s13277-016-5138-3

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