| Literature DB >> 33414520 |
Seisuke Tanigawa1,2, Mitsugu Fujita3, Chiami Moyama1, Shota Ando1, Hiromi Ii1, Yasushi Kojima4, Teruaki Fujishita4, Masahiro Aoki4,5, Hayato Takeuchi2, Takumi Yamanaka2, Yoshinobu Takahashi2, Naoya Hashimoto2, Susumu Nakata6.
Abstract
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.Entities:
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Year: 2021 PMID： 33414520 DOI： 10.1038/s41417-020-00282-5
Source DB: PubMed Journal: Cancer Gene Ther ISSN： 0929-1903 Impact factor: 5.987