 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 16, 2020 |
| Title |
ARS2/MAGL signaling in glioblastoma stem cells promotes self-renewal and M2-like polarization of tumor-associated macrophages I |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The interplay between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAMs) promotes progression of glioblastoma multiforme (GBM). However, the detailed molecular mechanisms underlying the relationship between these two cell types remain unclear. Here, we demonstrate that ARS2 (arsenite-resistance protein 2), a zinc finger protein that is essential for early mammalian development, plays critical roles in GSC maintenance and M2-like TAM polarization. ARS2 directly activates its novel transcriptional target MGLL, encoding monoacylglycerol lipase (MAGL), to regulate the self-renewal and tumorigenicity of GSCs through production of prostaglandin E2 (PGE2), which stimulates β-catenin activation of GSC and M2-like TAM polarization. Specific knockdown of ARS2 or MAGL significantly suppressed self-renewal and tumor growth, and increased survival in a mouse intracranial xenograft model of GSCs. We identify M2-like signature downregulated by which MAGL-specific inhibitor, JZL184, increased survival rate significantly in the mouse xenograft model by blocking PGE2 production. The M2-like signature is enriched in mesenchymal subtype and predicted poor survival in GBM patients. Taken together, our results suggest that blocking the interplay between GSCs and TAMs by targeting ARS2/MAGL signaling offers a potentially novel therapeutic option for GBM patients.
|
| |
|
| Overall design |
shARS
|
| |
|
| Citation(s) |
32532977 |
| |
| Submission date |
May 15, 2020 |
| Last update date |
Jun 22, 2020 |
| Contact name |
Young Taek Oh |
| E-mail(s) |
yt0625@gmail.com
|
| Organization name |
Samsung Medical Center
|
| Street address |
50 Irwon-dong, Gangnam-gu
|
| City |
Seoul |
| ZIP/Postal code |
135-710 |
| Country |
South Korea |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA633041 |
| SRA |
SRP261795 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE150630_shARS2_processed_data.txt.gz |
672.3 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
