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| Status |
Public on Feb 15, 2015 |
| Title |
Expression profile of osteosarcoma cells in which Sox2 maintains cancer stem cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Sox2 is required to maintain osteosarcoma cell tumor initiation.Knockdown of Sox2 leads tpo loss of tumorigenic properties. To examine gene expression changes upon Sox2 knockdown, we performed microarray analysis on mouse osteosarcoma cells expressing scrambled or Sox2shRNA. We found that genes upregulated upon Sox2 knockdown included osteoblast diffrentiation genes and genes down regulated included cell cycle and RNA processing genes as well as YAP-TEAD target genes.
The Hippo pathway has a profound tumor suppressive role in cancer by restraining the strong growth-promoting function of YAP. We have previously shown that the stem cell transcription factor Sox2 maintains the tumorigenicity of osteosarcoma cancer stem cells (CSCs). In this report, we describe that Sox2 maintains stemness by antagonizing the Hippo pathway via direct repression of Hippo activators, Nf2 (Merlin) and WWC1 (Kibra), thereby leading to exaggerated YAP function. YAP is potently oncogenic in osteosarcoma and its depletion sharply reduces the tumorigenic CSC fraction. Low Nf2, low WWC1, and high YAP expression mark the CSC fraction of the tumor population, while the more differentiated fraction has high Nf2, high WWC1 and reduced YAP expression. This Sox2-Hippo axis is conserved and also operates in other Sox2-dependent cancers such as glioblastomas. We propose that disruption of YAP transcriptional activity reduces CSCs and could be a therapeutic strategy for Sox2- dependent tumors.
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| Overall design |
Gene expression of 482 mouse lines mOS482 were analyzed by microarray. 3 replicates each of scrambled and Sox2shRNA were processed and hybridized
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| Contributor(s) |
Mansukhani A, BasuRoy U |
| Citation(s) |
25832504 |
| |
| Submission date |
Jan 14, 2015 |
| Last update date |
May 04, 2018 |
| Contact name |
Alka Mansukhani |
| E-mail(s) |
alka.mansukhani@nyumc.org
|
| Phone |
2122535906
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| Organization name |
New York University Medical Center
|
| Department |
Microbiology
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| Lab |
Basilico/Mansukhani
|
| Street address |
550 First Avenue
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
11101 |
| Country |
USA |
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| Platforms (1) |
| GPL8321 |
[Mouse430A_2] Affymetrix Mouse Genome 430A 2.0 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA272604 |
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