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Series GSE76422 Query DataSets for GSE76422
Status Public on Mar 07, 2017
Title Wnt5a Drives The State Transition To An Invasive Phenotype In Human Glioblastoma Cancer Stem Cells
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Numerous pathways underlie brain invasion by tumors, a critical element underpinning recurrence and lethality in human glioblastomas (hGBMs). The identification of the master factors that elicit these pathways globally, driving invasion altogether, eludes us. We report that high expression levels of non-canonical Wnt5a characterize the most invasive gliomas, epitomize dismal prognosis and discriminate the most infiltrating mesenchymal hGBMs from proneural and classical ones. Exacerbated Wnt5a defines mesenchymal hGBM cells (Wnt5aHigh) possessing prototypical invasiveness and tumor-promoting stem-like characteristics (TPCs), but not their Wnt5aLow siblings. While inhibition of Wnt5a suppresses infiltration in mesenchymal hGBM TPCs, administration or over-expression of Wnt5a elicits the opposite effects, turning on infiltrative “mesenchymal-like” molecular programs in poorly motile, classical hGBM TPCs and Wnt5aLow mesenchymal TPCs, ex vivo and intracranially. Anti-Wnt5a antibodies or antagonist Wnt5a peptides block invasion, increasing survival in clinically relevant intracranial hGBM models. Wnt5a emerges as a master regulator in gliomatous invasion, endowing hGBM TPCs with archetypal, infiltratory transcriptional and functional profiles, providing a unique target to tackle brain invasion by hGBM cancer stem cells.
 
Overall design A total of 12 samples were analyzed. Each experimental group was made of two biological replicates. Each biological replicate had two technical replicates. Sorted hGBM specimens were compared with unsorted hGBM specimens.
 
Contributor(s) Binda E, Mazza T, Vescovi AL
Citation(s) 28011620
Submission date Dec 30, 2015
Last update date Oct 29, 2018
Contact name Tommaso Mazza
Organization name IRCCS Casa Sollievo della Sofferenza
Department Bioinformatics
Street address Viale Cappuccini, 1
City S. Giovanni Rotondo (FG)
ZIP/Postal code 71013
Country Italy
 
Platforms (1)
GPL17586 [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]
Samples (12)
GSM2011223 Sorted mesenchymal hGBM23 specimen, WNT5A+ tech Rep 1
GSM2011224 Sorted mesenchymal hGBM23 specimen, WNT5A+ tech Rep 2
GSM2011225 Sorted mesenchymal hGBM23 specimen, WNT5A- tech Rep 1
Relations
BioProject PRJNA307251

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE76422_Additonal_Probeset_information.txt.gz 2.3 Kb (ftp)(http) TXT
GSE76422_HTA-2_0.na35.hg19.probeset.csv.zip.gz 52.7 Mb (ftp)(http) ZIP
GSE76422_HTA-2_0.na35.hg19.transcript.csv.gz 41.6 Mb (ftp)(http) CSV
GSE76422_RAW.tar 282.8 Mb (http)(custom) TAR (of CEL)
GSE76422_normalized_data_all_na35.hg19.txt.gz 2.8 Mb (ftp)(http) TXT
Processed data included within Sample table
Processed data are available on Series record

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