Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IGFBP2 driven glioma progression is prevented by blocking a clinically significant network of integrin, ILK, and NK-kB

ABSTRACT: Insulin-like growth factor-binding protein 2 (IGFBP2) is increasingly recognized as a glioma oncogene, emerging as a target for therapeutic intervention. In this study, we used an integrative approach to characterizing the IGFBP2 network, combining transcriptional profiling of human glioma with validation in glial cells and the replication competent ASLV long terminal repeat with a splice acceptor/tv-a glioma mouse system. We demonstrated that IGFBP2 expression is closely linked to genes in the integrin and integrin-linked kinase (ILK) pathways and that these genes are associated with prognosis. We further showed that IGFBP2 activates integrin β1 and down- stream invasion pathways, requires ILK to induce cell motility, and activates NF-κB. Most significantly, the IGFBP2/integrin/ILK/NF-κB network functions as a physiologically active signaling pathway in vivo by driving glioma progression; interfering with any point in the pathway markedly inhibits progression. The results of this study reveal a signaling pathway that is both targetable and highly relevant to improving the survival of glioma patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE35467 | GEO | 2012/02/02

SECONDARY ACCESSION(S): PRJNA152343

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

IGFBP2 driven glioma progression is prevented by blocking a clinically significant network of integrin, ILK, and NK-kB

Project description:Insulin-like growth factor-binding protein 2 (IGFBP2) is increasingly recognized as a glioma oncogene, emerging as a target for therapeutic intervention. In this study, we used an integrative approach to characterizing the IGFBP2 network, combining transcriptional profiling of human glioma with validation in glial cells and the replication competent ASLV long terminal repeat with a splice acceptor/tv-a glioma mouse system. We demonstrated that IGFBP2 expression is closely linked to genes in the integrin and integrin-linked kinase (ILK) pathways and that these genes are associated with prognosis. We further showed that IGFBP2 activates integrin ?1 and down- stream invasion pathways, requires ILK to induce cell motility, and activates NF-?B. Most significantly, the IGFBP2/integrin/ILK/NF-?B network functions as a physiologically active signaling pathway in vivo by driving glioma progression; interfering with any point in the pathway markedly inhibits progression. The results of this study reveal a signaling pathway that is both targetable and highly relevant to improving the survival of glioma patients. We performed cDNA microarray analysis to compare two stably expressing cell lines originating from SNB19; two clones expressing a mutant form of IGFBP2 that cannot bind integrin (RGD ? RGE point mutation; referred to as RGE mutant); and two clones expressing wild-type IGFBP2. SNB19 clones transfected with empty vector were placed in the reference channel in each hybridization.

2012-02-02 | E-GEOD-35467 | biostudies-arrayexpress

An ILK/STAT3 pathway controls plasticity in a neural stem cell model of glioblastoma.

Project description:Glioblastomas (GBM) are driven by malignant neural stem-like cells that display extensive heterogeneity and phenotypic plasticity, which drives tumour progression and therapeutic resistance. Here we show that the nodal extracellular matrix-cell adhesion protein integrin-linked kinase (ILK) is a key determinant of phenotypic plasticity and the mesenchymal-like, invasive cell state in mouse GBM stem cells. We found that an ILK-STAT3 signalling pathway is required for plasticity that enables the transition of GBM stem cells to an astrocyte-like state both in vitro andin vivo. GBM cells genetically depleted of ILK become predominantly stabilised in a transcriptionally-defined progenitor-like state that is characterised by lack of response to differentiation cues and constitutive proliferation. Loss of ILK or interference with STAT3 impairs differentiation potential, reducing phenotypic plasticity of tumour cell populations; additionally, ILK loss causes a mesenchymal- to epithelial-like morphological transition and suppression of malignancy-associated features. Our work defines ILK as a central regulator of multiple GBM phenotypes including phenotypic plasticity and mesenchymal state.

2023-08-07 | GSE240193 | GEO

Identifying alterations post ILK inhibition in Meningioma cell lines

Project description:The current study reports alterations in PI3-Akt and Focal adhesion pathway post ILK inhibition in meningioma cell lines. The inhibition is done using a pyrazole that specifically inhibits Integrin Link Kinase. The global proteomic profile was analysed post treatment (24 hours) in treated vs untreated cell line replicates.

2021-09-08 | PXD014855 | Pride

Crosstalk between the STAT3, NF-kB and Notch signaling pathways in glioblastoma stem cells

Project description:In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. We demonstrate that adherent glioma CSCs exhibit characteristics previously described for CSCs grown in suspension culture. The expression of CD133, Sox2 and Nestin increased when compared to glioma cells grown in monolayer, and the adherent CSCs were ~100 times more tumorigenic in vivo than monolayer cultured glioma cells. We also found that while the STAT3 and NF-κB signaling pathways are constitutively activated in glioma lines, these pathways are dramatically activated in glioma CSCs. Treatment with STAT3 inhibitors led to a loss of nuclear activation of STAT3 signaling and suppression of growth in both monolayer and CSC conditions. There was a markedly greater growth suppressive effect on glioma CSCs, suggesting that targeted therapy of these key pathways in glioma CSCs may be possible. To further investigate potential biomarkers in glioma CSCs, microarray analysis was performed and revealed deregulation of the Notch signaling pathway. This constitutive activation of STAT3, NF-κB, and Notch pathways in glioma CSCs helps identify novel therapeutic targets for the treatment of glioma. GBM6 cells were continuously maintained as subcutaneous xenografts in NSG mice, and monolayer and CSC cultures were derived from freshly harvested tumor tissue. A total of 6 samples were subjected to microarray analysis, with three biological replicates for each experimental condition.

2013-06-19 | E-GEOD-48079 | biostudies-arrayexpress

Homo sapiens

Project description:IGFBP2 driven glioma progression is prevented by blocking a clinically significant network of integrin, ILK, and NK-kB

| PRJNA152343 | ENA

Role of ILK in cardiac regeneration

Project description:Two different mouse models of cardiac-specific ILK expression (ILKS343D and ILKR211A) were used to investigate the role of ILK in cardiac regeneration

2012-12-25 | GSE25729 | GEO

Expression data from Integrin-linked kinase (ILK)-deficient epidermis

Project description:ILK is essential for proper development of hair follicles, and for epidermal integrity and repair after injury. To better understand the pathways modulated by ILK in the epidermis, we compared the transcriptomes of ILK-deficient and -expressing epidermis using microarray analyses. Ilktm1Star (with floxed Ilk alleles) and Tg(KRT14-cre)1Amc/J mice were bred, and the resulting mice were bred again with Ilktm1Star mice, to generate animals heterozygos for the KRT14-cre transgene and either heterozygous (ILK-expressing) or homozygous (ILK-deficient) for the floxed Ilk alleles. The epidermis of 3 day-old animals was harvested and used to prepare RNA for the microarrays. The animals used were littermates. RNA from the epidermis of five ILK-deficient and five ILK-expressing mice were used.

2012-01-18 | E-GEOD-35129 | biostudies-arrayexpress

Redox-Dependent Igfbp2 Signaling Controls Brca1 DNA Damage Response to Govern Neural Stem Cell Fate

Project description:Neural stem cell (NSC) maintenance and functions are regulated by reactive oxygen species (ROS). However, the mechanisms by which ROS control NSC behavior remain unclear. Here we report that ROS-dependent Igfbp2 signaling controls DNA repair pathways which balance NSC self-renewal and lineage commitment. Ncf1 or Igfbp2 deficiency constrained NSCs to a self-renewing state and prevented neurosphere formation due to absent Igfbp2 cysteine-43 oxidation. Ncf1-dependent oxidation of Igfbp2 promoted neurogenesis by NSCs in vitro and in vivo, while repressing Brca1 DNA damage response genes and inducing DNA double-strand breaks (DDSBs). By contrast, Ncf1–/– and Igfbp2–/– NSCs favored the formation of oligodendrocytes in vitro and in vivo. Notably, transient repression of Brca1 DNA repair pathway genes induced DDSBs and was sufficient to rescue the ability of Ncf1–/– and Igfbp2–/– NSCs to lineage-commit to form neurospheres and neurons. Our study highlights the role of DNA damage/repair in orchestrating NSC fate decisions downstream of redox-regulated Igfbp2.

2023-01-17 | GSE221955 | GEO

Expression data from Integrin-linked kinase (ILK)-deficient epidermis

2012-01-18 | GSE35129 | GEO

Crosstalk between the STAT3, NF-kB and Notch signaling pathways in glioblastoma stem cells

2013-06-19 | GSE48079 | GEO