GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE73999 Query DataSets for GSE73999
Status Public on Dec 02, 2019
Title P120-catenin dependent glioma-cell networks drive growth and diffuse brain infiltration
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The poor prognosis of diffuse gliomas is the consequence of adaptive growth and survival programs coupled to their unsurmountable capacity to infiltrate the brain. Diffuse brain infiltration is a particularly detrimental hallmark of gliomas, however the underlying cellular and signaling mechanisms remain elusive. Histological analysis of glioma samples suggests brain invasion by individual glioma cells extending along blood vessels and nerve tracts, consistent with individual-cell growth and invasion programs. However, using thick 3D tissue sections, we here show that human diffuse gliomas consist of multicellular networks in both tumor center and invasion region. This was confirmed in three orthotopic human glioma xenograft models in mouse brain reflecting neuronal, proneural and mesenchymal subtypes. The connections between glioma cells are provided by either branched filamentous protrusions connecting cells across distance or epithelial-like linear adherens junctions between directly adjacent cells. These intercellular contacts showed dynamic turn-over kinetics, which enabled intercellularly synchronized calcium signaling waves, directionally persistent migration as network and network plasticity. Interference with the stability of adherens junction by downregulating p120-catenin causes irreversibly compromised cell-cell interaction, near-complete inhibition of diffuse brain infiltration and a severe growth defect and marginalized microlesions as outcome. Mining of human glioma cohorts revealed an inverse association of p120 with patient survival and, using next-generation RNA sequencing, profound cell reprogramming with perturbed cell adhesion and axonal guidance pathways was uncovered after p120 downregulation. In conclusion, reminiscent of neuronal and glial progenitor programs during morphogenesis and repair, diffuse gliomas progress as neuronal-like, collective network the subunits of which cooperate by complex cell-cell signaling to promote cell growth and detrimental brain infiltration. Targeting adherens junctions and cell-cell cooperation thus represent unanticipated therapeutic principles to prevent glioma progression.
Overall design Transcriptome RNAseq profile of 6 samples of glioma cell lines of p120-kd and NT-shRNA samples, two replicates for each
Contributor(s) Gritsenko P, Atlasy N, Dieteren C, Navis A, Venhuizen J, Veelken C, Schubert D, Acker-Palmer A, Westerman B, Wurdinger T, Leenders W, Wesseling P, Stunnenberg H, Friedl P
Citation(s) 31907411
Submission date Oct 14, 2015
Last update date Mar 02, 2020
Contact name Nader Atlasy
Organization name Radboud University
Department Molecular Biology
Lab Henk Stunnenberg
Street address Geert Grooteplein 28
City Nijmegen
State/province Gerderland
ZIP/Postal code 6500 HB
Country Netherlands
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (12)
GSM1907885 U251_NT
GSM1907886 U251_NT.1
GSM1907887 U251_KD
BioProject PRJNA298692
SRA SRP064795

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 2.2 Mb (ftp)(http) TXT
GSE73999_E468_NT_KD.Downregulated.genes.xls.gz 138.7 Kb (ftp)(http) XLS
GSE73999_E468_NT_KD.Upregulated.genes.xls.gz 64.7 Kb (ftp)(http) XLS
GSE73999_E98_NT_KD.Downregulated.genes.xls.gz 147.0 Kb (ftp)(http) XLS
GSE73999_E98_NT_KD.Upregulated.genes.xls.gz 96.8 Kb (ftp)(http) XLS
GSE73999_U251_NT_KD.Downregulated.genes.xls.gz 7.9 Kb (ftp)(http) XLS
GSE73999_U251_NT_KD.Upregulated.genes.xls.gz 33.4 Kb (ftp)(http) XLS
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap