Tumor Biology

, Volume 37, Issue 10, pp 13777–13788 | Cite as

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

Original Article

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.

Keywords

Neuropilin-1 GIPC1 Gene therapy Glioma 

Notes

Acknowledgments

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

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Guilong Zhang
    • 1
  • Lukui Chen
    • 1
  • Kouhong Sun
    • 2
  • Ahsan Ali Khan
    • 1
  • Jianghua Yan
    • 3
  • Hongyi Liu
    • 4
  • Ailin Lu
    • 5
  • Ning Gu
    • 6
  1. 1.Department of Neurosurgery, Zhongda Hospital, School of MedicineSoutheast UniversityNanjingChina
  2. 2.Nanjing Zoonbio BiotechnologyNanjingChina
  3. 3.Cancer Research CenterXiamen UniversityXiamenChina
  4. 4.Department of NeurosurgeryNanjing Brain HospitalNanjingChina
  5. 5.Department of NeurosurgeryJiangsu Province HospitalNanjingChina
  6. 6.School of Biological Science and Medical EngineeringSoutheast UniversityNanjingChina

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