Inhibition of Gli2 suppresses tumorigenicity in glioblastoma stem cells derived from a de novo murine brain cancer model.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
26
08
2020
accepted:
04
12
2020
revised:
26
11
2020
pubmed:
9
1
2021
medline:
3
3
2022
entrez:
8
1
2021
Statut:
ppublish
Résumé
The prognosis of glioblastoma remains poor despite intensive research efforts. Glioblastoma stem cells (GSCs) contribute to tumorigenesis, invasive capacity, and therapy resistance. Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a stem cell marker, is involved in the maintenance of GSCs, although the properties of Lgr5-positive GSCs remain unclear. Here, the Sleeping-Beauty transposon-induced glioblastoma model was used in Lgr5-GFP knock-in mice identify GFP-positive cells in neurosphere cultures from mouse glioblastoma tissues. Global gene expression analysis showed that Gli2 was highly expressed in GFP-positive GSCs. Gli2 knockdown using lentiviral-mediated shRNA downregulated Hedgehog-related and Wnt signaling pathway-related genes, including Lgr5; suppressed tumor cell proliferation and invasion capacity; and induced apoptosis. Pharmacological Gli inhibition with GANT61 suppressed tumor cell proliferation. Silencing Gli2 suppressed the tumorigenicity of GSCs in an orthotopic transplantation model in vivo. These findings suggest that Gli2 affects the Hedgehog and Wnt pathways and plays an important role in GSC maintenance, suggesting Gli2 as a therapeutic target for glioblastoma treatment.
Identifiants
pubmed: 33414520
doi: 10.1038/s41417-020-00282-5
pii: 10.1038/s41417-020-00282-5
doi:
Substances chimiques
Gli2 protein, mouse
0
Zinc Finger Protein Gli2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1339-1352Subventions
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 20K07623
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 16K08722
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.
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