Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe

ABSTRACT: Glioblastoma ranks among the most lethal of primary brain malignancies, with glioblastoma stem cells (GSCs) at the apex of tumor cellular hierarchies. Here, to discover novel therapeutic GSC targets, we interrogated gene expression profiles from GSCs, differentiated glioblastoma cells (DGCs), and neural stem cells (NSCs), revealing EYA2 as preferentially expressed by GSCs. Targeting EYA2 impaired GSC maintenance and induced cell cycle arrest, apoptosis, and loss of self-renewal. EYA2 displayed novel localization to centrosomes in GSCs, and EYA2 tyrosine (Tyr) phosphatase activity was essential for proper mitotic spindle assembly and survival of GSCs. Inhibition of the EYA2 Tyr phosphatase activity, via genetic or pharmacological means, mimicked EYA2 loss in GSCs in vitro and extended the survival of tumor-bearing mice. Supporting the clinical relevance of these findings, EYA2 portends poor patient prognosis in glioblastoma. Collectively, our data indicate that EYA2 phosphatase function plays selective critical roles in the growth and survival of GSCs, potentially offering a high therapeutic index for EYA2 inhibitors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE135306 | GEO | 2021/09/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Silencing of PFKFB4 in Glioblastoma Stem-like Cells

Project description:In order to investigate the crucial role of PFKFB4 in glioblastoma stem-like cell (GSC) survival, gene expression microarray-based transcriptome analysis was conducted on GSCs transduced for 4 days with PFKFB4 shRNA compared with GSCs transduced with shNT.

2019-01-05 | GSE108742 | GEO

Gene Expression Profiling in PRKCI vs NT-silenced Cells

Project description:In order to investigate the crucial role of PRKCI in glioblastoma stem-like cell (GSC) survival, gene expression microarray-based transcriptome analysis was conducted on GSCs transduced for 4 days with PRKCI shRNA compared with GSCs transduced with shNT.

2016-01-21 | GSE77030 | GEO

Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe

Project description:Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe

| PRJNA558360 | ENA

Transcriptome analysis of EYA2 non-expressing pancreatic cancer cell lines with stable transfectant overexpressing EYA2

Project description:Transcriptome analysis of EYA2 non-expressing pancreatic cancer cell lines with stable transfectant overexpressing EYA2

2012-06-30 | GSE33282 | GEO

Ion Channel Expression Patterns in Glioblastoma Stem Cells with Functional and Therapeutic Implications for Malignancy

Project description:Ion channels and transporters have increasingly recognized roles in cancer progression through the regulation of cell proliferation, migration, and death. Glioblastoma stem-like cells (GSCs) are a source of tumor formation and recurrence in glioblastoma multiforme, a highly aggressive brain cancer, suggesting that ion channel expression may be perturbed in this population. However, little is known about the expression and functional relevance of ion channels that may contribute to GSC malignancy. Using RNA sequencing, we assessed the enrichment of ion channels in GSC isolates and non-tumor neural cell types. We identified a unique set of GSC-enriched ion channels using differential expression analysis that stratify by molecular subtype and are associated with distinct gene mutation signatures. In support of potential clinical relevance, expression of selected GSC-enriched ion channels evaluated in human glioblastoma databases of The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project correlated with patient survival times. Finally, genetic knockdown or pharmacological inhibition of individual or classes of GSC-enriched ion channels constrained growth of GSCs compared to normal neural stem cells. This first-in-kind global examination characterizes ion channels enriched in GSCs and explores their potential clinical relevance to glioblastoma molecular subtypes, gene mutations, survival outcomes, regional tumor expression, and experimental responses to loss-of-function. Together, the data support the potential biological and therapeutic impact of ion channels on GSC malignancy and provide strong rationale for further examination of their mechanistic and therapeutic importance.

2017-04-21 | GSE89623 | GEO

Morphoregulatory ADD3 underlies glioblastoma growth and formation of tumor-tumor connections

Project description:Glioblastoma is a major unmet clinical need characterized by striking inter- and intra-tumoral heterogeneity and a population of glioblastoma stem cells (GSCs), conferring aggressiveness and therapy resistance. GSCs communicate through a network of tumor-tumor connections (TTCs), including nanotubes and microtubes, promoting tumor progression. However, very little is known about the mechanisms underlying TTC formation and overall GSC morphology. As GSCs closely resemble neural progenitor cells during neurodevelopment, we hypothesised that GSCs’ morphological features affect tumour progression. We identified GSC morphology as a new layer of tumoral heterogeneity with important consequences on GSC proliferation. Strikingly, we showed that the neurodevelopmental morphoregulator ADD3, is sufficient and necessary for maintaining proper GSC morphology, TTC abundance and cell cycle progression as well as required for cell survival. Remarkably, both the effects on cell morphology and proliferation depend on the stability of actin cytoskeleton. Hence, cell morphology and its regulators play a key role in tumor progression by mediating cell-cell communication. We thus propose that GSC morphological heterogeneity holds the potential to identify new therapeutic targets and diagnostic markers.

2024-11-12 | GSE280761 | GEO

Transcriptome analysis of EYA2 non-expressing pancreatic cancer cell lines with stable transfectant overexpressing EYA2

Project description:Transcriptome analysis of EYA2 non-expressing pancreatic cancer cell lines with stable transfectant overexpressing EYA2 We analyzed Panc2.5 and Panc3.014 stable transfectant (overexpressing EYA2) and control (empty pcDNA6.2/cLumio-DEST vector) cell transcriptomes using the Affymetrix Exon Array ST1.0 platform. Statistical analysis of gene expression array data was completed with Partek Genomic Suite 6.4 software.

2012-06-29 | E-GEOD-33282 | biostudies-arrayexpress

Identification and molecular characterization of distinct glioblastoma cancer stem cell populations

Project description:Malignant glioblastoma (GBM) is a highly aggressive brain tumor with a dismal prognosis and limited therapeutic options. Genomic profiling of GBM samples in the TCGA database has identified four molecular subtypes (Proneural, Neural, Classical and Mesenchymal), which may arise from different glioblastoma stem-like cell (GSC) populations. In the present study, we identify two GSC populations that produce GBM tumors by subcutaneous and intracranial injection with identical histological features. Gene expression analysis revealed that xenografts of GSCs grown as spheroid cultures had a Classical molecular subtype similar to that of bulk tumor cells. In contrast xenografts of GSCs grown as adherent cultures on laminin-coated plates expressed a Mesenchymal gene signature. Adherent GSC-derived xenografts had high STAT3 and ANGPTL4 expression as well as enrichment for stem cell markers, transcriptional networks and pro-angiogenic markers characteristic of the Mesenchymal subtype. Examination of clinical samples from GBM patients showed that STAT3 expression was directly correlated with ANGPTL4 expression, and that increased expression of these genes correlated with poor patient survival and performance. A pharmacological STAT3 inhibitor abrogated STAT3 binding to the ANGPTL4 promoter and exhibited anticancer activity in vivo. Taken together, we identified two distinct GSC populations that produce histologically identical tumors but with very different gene expression patterns, and a STAT3/ ANGPTL4 pathway in glioblastoma that may serve as a target for therapeutic intervention. 2 samples of each variable were analyzed. Cells were cultured under normal adherent conditon (Bulk tumor cells), non-adherent plates with stem cell medium (Sp-GSC) or laminin-coated plates with stem cell medium (Ad-GSC). Xenografts were generated in NSG mice by subcutaneous inoculation.

2015-07-01 | E-GEOD-65576 | biostudies-arrayexpress

Transforming growth factor β (TGFβ) and BMP7 regulate glioblastoma stem cells differentiation status

Project description:Glioblastoma stem cells (GSCs) fate is controlled by environmental cues, among which cytokines play a crucial role. The transforming growth factor β (TGFβ) family signaling pathways controls GSCs. On one hand, TGFβ promotes cell proliferation in GBM, it induces the expression of platelet-derived growth factor-B (PDGFB). Moreover, TGFβ, via its signaling mediators Smad2/3, induces the expression of the cytokine leukemia inhibitory factor (LIF) and Sox4, which in turn enhances the expression of the stem cell transcription factor Sox2; this increases the self-renewal capacity of the GSCs and their stemness characteristics, and enhances the GSC tumor-initiating potential. On the other hand, Bone morphogenic proteins (BMPs) are known to promote GSC differentiation towards the astrocytic phenotype. To further understand which genes are regulated by TGFβ and BMP7 in GSCs we performed a microarray in the Affymetrix HTA2 platform in three different glioblastoma cell line, U2987, and two patient-derived glioblastoma stem cells, U3031MG and U3034MG, in the presence or absence of 5 ng/ml of TGFβ or 30 ng/ml BMP7 for 24 h, three biological replicates per condition.

2020-09-01 | E-MTAB-9076 | biostudies-arrayexpress

Sorting nexin 10 sustains platelet-derived growth factor receptor signaling in glioblastoma stem cells via endosomal protein sorting

Project description:Glioblastoma is the most malignant primary brain tumor for which the prognosis is still dismal despite aggressive surgical, medical, and radiation therapies. Glioblastoma stem cells (GSCs) promote therapeutic resistance and cellular heterogeneity due to their self-renewal properties and capacity for plasticity. To understand the molecular processes essential for maintaining GSCs, we performed an integrative analysis comparing active enhancer landscapes, transcriptional profiles, and functional genomics profiles of GSCs and non-neoplastic neural stem cells (NSCs). We identified sorting nexin 10 (SNX10), an endosomal protein sorting factor, as selectively expressed in GSCs compared to NSCs and essential for GSC survival. Targeting SNX10 impaired GSC viability and proliferation, induced apoptosis, and reduced self-renewal capacity. Mechanistically, GSCs utilized endosomal protein sorting to promote platelet-derived growth factor receptor β (PDGFRβ) proliferative and stem cell signaling pathways via post-transcriptional regulation of the PDGF receptor tyrosine kinase. Targeting SNX10 expression extended survival of orthotopic xenograft-bearing mice, and high SNX10 expression correlated with poor glioblastoma patient prognosis, suggesting its potential clinical importance. Thus, our study reveals an essential connection between endosomal protein sorting and oncogenic receptor tyrosine kinase signaling and suggests that targeting endosomal sorting may represent a promising therapeutic approach for glioblastoma treatment.

2023-03-31 | GSE221714 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data