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dc.contributor.authorEuskirchen, Philippen_US
dc.contributor.authorRadke, Josefineen_US
dc.contributor.authorSchmidt, Marc Sörenen_US
dc.contributor.authorHeuling, Eva Schulzeen_US
dc.contributor.authorKadikowski, Ericen_US
dc.contributor.authorMaricos, Meronen_US
dc.contributor.authorKnab, Felixen_US
dc.contributor.authorGrittner, Ulrikeen_US
dc.contributor.authorZerbe, Normanen_US
dc.contributor.authorCzabanka, Marcusen_US
dc.contributor.authorDieterich, Christophen_US
dc.contributor.authorMiletic, Hrvojeen_US
dc.contributor.authorMørk, Sverreen_US
dc.contributor.authorKoch, Arenden_US
dc.contributor.authorEndres, Matthiasen_US
dc.contributor.authorHarms, Christophen_US
dc.PublishedEuskirchen P, Radke, Schmidt, Heuling, Kadikowski, Maricos, Knab, Grittner, Zerbe, Czabanka, Dieterich C, Miletic H, Mørk S, Koch, Endres M, Harms. Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma. PLoS ONE. 2017;12(9):e0185376eng
dc.description.abstractThe transcription factor ZEB1 has gained attention in tumor biology of epithelial cancers because of its function in epithelial-mesenchymal transition, DNA repair, stem cell biology and tumor-induced immunosuppression, but its role in gliomas with respect to invasion and prognostic value is controversial. We characterized ZEB1 expression at single cell level in 266 primary brain tumors and present a comprehensive dataset of high grade gliomas with Ki67, p53, IDH1, and EGFR immunohistochemistry, as well as EGFR FISH. ZEB1 protein expression in glioma stem cell lines was compared to their parental tumors with respect to gene expression subtypes based on RNA-seq transcriptomic profiles. ZEB1 is widely expressed in glial tumors, but in a highly variable fraction of cells. In glioblastoma, ZEB1 labeling index is higher in tumors with EGFR amplification or IDH1 mutation. Co-labeling studies showed that tumor cells and reactive astroglia, but not immune cells contribute to the ZEB1 positive population. In contrast, glioma cell lines constitutively express ZEB1 irrespective of gene expression subtype. In conclusion, our data indicate that immune infiltration likely contributes to differential labelling of ZEB1 and confounds interpretation of bulk ZEB1 expression data.en_US
dc.rightsAttribution CC BYeng
dc.titleCellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastomaen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2017 The Author(s)
dc.source.journalPLoS ONE

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