Detailed Information

Cited 20 time in webofscience Cited 18 time in scopus
Metadata Downloads

PARK7 maintains the stemness of glioblastoma stem cells by stabilizing epidermal growth factor receptor variant III

Authors
Kim, Jeong-YubKim, Hee-JinJung, Chan-WoongChoi, Byung-IlLee, Dae-HeePark, Myung-Jin
Issue Date
Jan-2021
Publisher
Nature Publishing Group
Citation
Oncogene, v.40, no.3, pp 508 - 521
Pages
14
Indexed
SCIE
SCOPUS
Journal Title
Oncogene
Volume
40
Number
3
Start Page
508
End Page
521
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/51601
DOI
10.1038/s41388-020-01543-1
ISSN
0950-9232
1476-5594
Abstract
PARK7 is involved in many key cellular processes, including cell proliferation, transcriptional regulation, cellular differentiation, oxidative stress protection, and mitochondrial function maintenance. Deregulation of PARK7 has been implicated in the pathogenesis of various human diseases, including cancer. Here, we aimed to clarify the effect of PARK7 on stemness and radioresistance of glioblastoma stem cells (GSCs). Serum differentiation and magnetic cell sorting of GSCs revealed that PARK7 was preferentially expressed in GSCs rather than differentiated GSCs. Immunohistochemical staining showed enhanced expression of PARK7 in glioma tissues compared to that in normal brain tissues. shRNA-mediated knockdown of PARK7 inhibited the self-renewal activity of GSCs in vitro, as evidenced by the results of neurosphere formation, limiting dilution, and soft-agar clonogenic assays. In addition, PARK7 knockdown suppressed GSC invasion and enhanced GSC sensitivity to ionizing radiation (IR). PARK7 knockdown suppressed expression of GSC signatures including nestin, epidermal growth factor receptor variant III (EGFRvIII), SOX2, NOTCH1, and OCT4. Contrarily, overexpression of PARK7 in CD133(-) non-GSCs increased self-renewal activities, migration, and IR resistance, and rescued the reduction of GSC factors under shPARK7-transfected and serum-differentiation conditions. Intriguingly, PARK7 acted as a co-chaperone of HSP90 by binding to it, protecting EGFRvIII from proteasomal degradation. Knockdown of PARK7 increased the production of reactive oxygen species, inducing partial apoptosis and enhancing IR sensitivity in GSCs. Finally, PARK7 knockdown increased mouse survival and IR sensitivity in vivo. Based on these data, we propose that PARK7 plays a pivotal role in the maintenance of stemness and therapeutic resistance in GSCs.
Files in This Item
There are no files associated with this item.
Appears in
Collections
4. Research institute > Institute for Trauma Research > 1. Journal Articles

qrcode

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

Altmetrics

Total Views & Downloads

BROWSE