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Series GSE99045 Query DataSets for GSE99045
Status Public on Aug 11, 2017
Title Targeting neuronal activity-regulated neuroligin-3 dependency for high-grade glioma therapy
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Neuronal activity promotes high-grade glioma (HGG) growth. An important mechanism mediating this neural regulation of brain cancer is activity-dependent cleavage and secretion of the synaptic molecule and glioma mitogen neuroligin-3 (Nlgn3), but the therapeutic potential of targeting Nlgn3 in glioma remains to be defined. We demonstrate a striking dependence of HGG growth on microenvironmental Nlgn3 and determine a targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma, diffuse intrinsic pontine glioma and adult glioblastoma fail to grow in Nlgn3 knockout mice. Glioma exposure to Nlgn3 results in numerous signaling consequences, including early focal adhesion kinase activation upstream of PI3K-mTOR. Nlgn3 is cleaved from both neurons and oligodendrocyte precursor cells via the ADAM10 sheddase. Administration of ADAM10 inhibitors robustly blocks HGG xenograft growth. This work defines the therapeutic potential of and a promising strategy for targeting Nlgn3 secretion in the glioma microenvironment, which could prove transformative for treatment of HGG.
Overall design RNA-seq patient-derived pediatric GBM cell cultures in two replicates. Libraries were sequenced on Illumina NextSeq 500, 1x75.
Contributor(s) Nagaraja S, Monje MM
Citation(s) 28959975
Submission date May 18, 2017
Last update date May 15, 2019
Contact name Michelle Monje
Organization name Stanford University
Street address 265 Campus Drive, SIM1 G3035
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (4)
GSM2631359 su-pcgbm2-dmso.1
GSM2631360 su-pcgbm2-dmso.2
GSM2631361 su-pcgbm2-nlgn3.1
BioProject PRJNA387119
SRA SRP107299

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Supplementary file Size Download File type/resource
GSE99045_su-pcgbm2-dmso.fpkm.featureCounts.txt.gz 471.2 Kb (ftp)(http) TXT
GSE99045_su-pcgbm2-nlgn3.fpkm.featureCounts.txt.gz 466.8 Kb (ftp)(http) TXT
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