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Abstract
Nogo receptor (NgR) has been shown to inhibit the migration and invasion of human glioma cells. However, little is known regarding the regulatory mechanisms of NgR in glioblastoma multiforme (GBM). In this study, we propose a novel mechanism that regulates the maturation process of NgR through an interaction with vimentin. The inhibition of TGFβ1 activity by LY2109761 attenuated the migration/invasion of GBM cells by upregulating cell-surface NgR. Conversely, the treatment of GBM cells with TGFβ1 suppressed NgR maturation. We showed that NgR and vimentin interact, which could be a possible mechanism for the suppression of NgR maturation. The knockdown of vimentin suppressed the migration/invasion of GBM cells through the increased maturation of NgR. Finally, TCGA (The Cancer Genome Atlas) analysis also supported the association of NgR and vimentin. The maturation of NgR is regulated by the interaction of vimentin and NgR, which attenuates the invasive activity of GBM, and might be a potential therapeutic target for brain cancer.
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1 Eulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, Korea; Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, Korea
2 Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, Korea
3 Specific Organs Cancer Branch, Research Institute and Hospital, National Cancer Center, Koyang, Korea
4 Divisions of Radiation Cancer Research, Research Center for Radio-Senescence, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
5 Immunotherapy Convergence Research Group, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
6 Eulji Biomedical Science Research Institute, Eulji University School of Medicine, Daejeon, Korea; Department of Neurosurgery, Eulji University School of Medicine, Daejeon, Korea