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| Status |
Public on Aug 21, 2019 |
| Title |
A HIF-1α/Wnt signaling-dependent control of gene transcription regulates neuronal differentiation of glioblastoma stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
HIF-1α plays a crucial role in sustaining glioblastoma (GBM) cell growth and the maintenance of their undifferentiated phenotype. However, HIF-1α has been suggested to interplay with Wnt signaling components, thus activating a neuronal differentiation process in both GBM and normal brain. Here, we show that a β-catenin/TCF1/HIF-1α complex directly controls the transcription of neuronal differentiation genes in hypoxia. Conversely, at higher oxygen levels, the increased expression of TCF4 exerts a transcriptional inhibitory function on the same genomic regions, thus counteracting differentiation. Moreover, we demonstrate the existence of a positive correlation between HIF-1α, TCF1 and neuronal phenotype in GBM tumors, accompanied by the over-expression of several Wnt signaling components, finally impacting on patient prognosis. In conclusion, we unveil a mechanism by which TCF1 and HIF-1α induce a reminiscent neuronal differentiation of hypoxic GBM cells, which is hampered, in normoxia, by high levels of TCF4, thus de facto sustaining cell aggressiveness.
In this study we unveil a tightly regulated mechanism by which HIF-1α controls the balance of Wnt signaling co-factors and how their molecular interplay regulates the peculiar transcriptional events responsible for the phenotypic shift of GBM stem cells toward a reminiscent neuronal differentiation, which might represent a future potential strategy to therapeutically weaken their aggressiveness.
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| Overall design |
Gene expression was measured on Clariom S platform of cells derived from internal or periphery region of GBM tumors of 4 primary samples.
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| Contributor(s) |
Bresolin S, Persano L |
| Citation(s) |
31410187 |
| Submission date |
Apr 23, 2018 |
| Last update date |
Aug 21, 2019 |
| Contact name |
silvia bresolin |
| E-mail(s) |
silvia.bresolin@unipd.it
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| Phone |
+390498215487
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| Organization name |
università di padova
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| Department |
department of women's and children's health
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| Lab |
SSD ematologia-clinica sperimentale
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| Street address |
via giustiniani 3
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| City |
padova |
| State/province |
padova |
| ZIP/Postal code |
35128 |
| Country |
Italy |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA451418 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113512_RAW.tar |
8.7 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE113512_complete_normalized_data_including_control_probes.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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