Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma

Authors
Hong, Jun-HeeKang, SangjoSa, Jason K.Park, GunwooOh, Young TaekKim, Tae HoonYin, JinlongKim, Sung SooD'Angelo, FulvioKoo, HarimYou, YeonheePark, SaewhanKwon, Hyung JoonKim, Chan IlRyu, HaseoLin, WeiweiPark, Eun JungKim, Youn-JaePark, Myung-JinKim, HyunggeeKim, Mi-SukChung, SeokPark, Chul-KeePark, Sung-HyeKang, Yun HeeKim, Jong HeonSaya, HideyukiNakano, IchiroGwak, Ho-ShinYoo, HeonLee, JeongwuHur, Eun-MiShi, BingyangNam, Do-HyunIavarone, AntonioLee, Seung-HoonPark, Jong Bae
Issue Date
2월-2021
Publisher
OXFORD UNIV PRESS
Keywords
glioblastoma; myelin-associated infiltration; radiogenomics; nogo receptor
Citation
BRAIN, v.144, pp.636 - 654
Indexed
SCIE
SCOPUS
Journal Title
BRAIN
Volume
144
Start Page
636
End Page
654
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/129325
DOI
10.1093/brain/awaa433
ISSN
0006-8950
Abstract
As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.
Files in This Item
There are no files associated with this item.
Appears in
Collections
Graduate School > Department of Biotechnology > 1. Journal Articles
College of Engineering > Department of Mechanical Engineering > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Chung, Seok photo

Chung, Seok
공과대학 (기계공학부)
Read more

Altmetrics

Total Views & Downloads

BROWSE