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| Status |
Public on Oct 17, 2021 |
| Title |
Stat5b inhibition blocks proliferation and tumorigenicity of 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 |
Glioblastoma (GBM) is the most common and malignant type of brain cancer in adults with poor prognosis. GBM stem cells (GSCs) reside within niches in GBM tissues and contributes to recurrence and therapy resistance. Previous studies have shown that expression of leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5), a Wnt pathway-related stem cell marker, correlates with a poor prognosis in GBM, and its knockdown in GSCs induces apoptosis accompanied with downregulation of signal transducer and activator of transcription 5b (Stat5b). Here, we show that Stat5b co-localizes with Lgr5 in hypoxia-inducible factor 2α (Hif2α)-positive regions in GBM tissues. Functional analyses using GSCs derived from a murine de novo GBM model induced by oncogenic genes transduction using the Sleeping-Beauty transposon system revealed that expression of Stat5b was induced by culturing under hypoxia together with Lgr5, repressed by Hif2α knockdown, and reduced by Lgr5 knockdown or a Wnt/β-catenin signaling inhibitor ICG-001 treatment. Stat5b inhibition in the GSCs induced apoptosis and caused downregulation of Cyclin E2 resulted in blockade of entry into S-phase in the cell cycle. Disruption of Stat5b in an orthotopic transplantation model significantly prolongs event-free survival. These results suggest that Stat5b, regulated by hypoxia and the Wnt pathway, plays an important role in the maintenance and tumorigenicity of GSCs and may be a promising therapeutic molecular target to attack GSCs.
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| Overall design |
To test the effect of suppression of Stat5b on the gene expression, murine GSC was tranducted with lentiviral non-target (control) or Stat5b shRNA. Stat5b-knockdown GSCs were compared to control cells.
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| Contributor(s) |
Moyama C, Fujita M, Ando S, Taniguchi K, Ii H, Tanigawa S, Hashimoto N, Nakata S |
| Citation missing |
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| Submission date |
Oct 13, 2021 |
| Last update date |
Oct 20, 2021 |
| Contact name |
Chiami Moyama |
| E-mail(s) |
chiami0880@gmail.com
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| Organization name |
Kyoto Pharmaceutical University
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| Street address |
Misasagi-Nakauchicho 5, Yamashina-ku
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| City |
kyoto |
| ZIP/Postal code |
607-8414 |
| 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 |
PRJNA771077 |
