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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 20, 2020 |
| Title |
Inhibition of Gli2 suppresses tumorigenicity in glioblastoma stem cells derived from a de novo murine brain cancer model |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Prognosis of glioblastoma remains poor despite a great deal of research. In glioblastoma, the existence of glioblastoma stem cells (GSCs) has been shown, which are responsible for tumorigenesis, invasive capacity, and therapy resistance. One of cancer stem cell markers, Leucine-rich repeat-containing G-protein coupled receptor (Lgr5) plays a role in maintenance of GSCs, however, properties of the Lgr5 positive GSCs have not been fully understood. We applied the Sleeping-Beauty transposon-induced glioblastoma model to the Lgr5-GFP transgenic mice and sorted the GFP-positive cells from the neurosphere cultures derived from the mouse glioblastoma tissues. We found that the GFP-positive GSCs exhibited higher expression of Gli2 using a global gene expression analysis. Gli2 knockdown using lentiviral-mediated shRNA downregulates both the Hedgehog- and Wnt signaling pathway-related genes including Lgr5, suppresses tumor cell proliferation and invasion capacity, and induces apoptosis. Pharmacological Gli inhibition by GANT61 also suppresses tumor cell proliferation. Furthermore, the orthotopic transplantation model revealed that silencing of Gli2 suppresses tumorigenicity of GSCs in vivo. These findings demonstrate that Gli2 affects not only Hh pathway but also Wnt pathway and plays an important role in the GSC maintenance, suggesting that Gli2 may be a potential therapeutic target for glioblastoma treatment.
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| Overall design |
To test the effect of suppression of Gli2 on the gene expression, murine GSC was tranducted with lentiviral non-target (control) or Gli2 shRNA. Gli2-knockdown GSCs were compared to control cells.
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| Contributor(s) |
Tanigawa S, Fujita M, Moyama C, Ando S, Li H, Ashihara E, Kojima Y, Fujishita T, Aoki M, Takeuchi H, Yamanaka T, Takahashi Y, Hashimoto N, Nakata S |
| Citation missing |
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| Submission date |
Aug 19, 2020 |
| Last update date |
Aug 22, 2020 |
| Contact name |
Seisuke Tanigawa |
| E-mail(s) |
tanigawa@koto.kpu-m.ac.jp
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| Organization name |
Kyoto prefectural university of medicine
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| Department |
Neurosurgery
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| Street address |
465 Kajii-cho,Kawaramachi-Hirokoji
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| City |
Kyoto city |
| State/province |
Kyoto |
| ZIP/Postal code |
602-8566 |
| Country |
Japan |
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| Platforms (1) |
| GPL21163 |
Agilent-074809 SurePrint G3 Mouse GE v2 8x60K Microarray [Probe Name version] |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA658156 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156522_RAW.tar |
17.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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