Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA152343 | ENA |
REPOSITORIES: ENA
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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
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 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.
2012-02-02 | GSE35467 | GEO
Project description:Invasion of leukocytes, including neutrophils, in response to injury or infection relies on the orchestrated activation of integrins. The neutrophil integrin lymphocyte function-associated antigen-1 (LFA-1) has been implicated in the regulation of leukocyte adhesion by binding to ICAM-1 expressed on activated endothelial cells. The activation-dependent conformational change of LFA-1 to the high affinity conformation (H+) requires kindlin-3 binding to the tail of the β2-integrin. How the integrin linked kinase (ILK) affects activation of β2-integrins in leukocytes is currently unknown. Here, utilizing in vitro microfluidic adhesion chambers with conformation specific antibodies for neutrophil-like HL-60 cells, we show that knockdown of ILK reduces the conformational change of β2-integrins to the H+ conformation. Consequently, ILK-deficient mice show defects of leukocyte adhesion and recruitment in a chemokine and integrin-dependent cremaster muscle model and in a clinically relevant model of renal-ischemia-reperfusion-injury. Absence of protein kinase C (PKC)-α, which is known to phosphorylate Kindlin-3, reproduces such phenotype in bone marrow chimeric mice. ILK is required for chemokine-induced upregulation of PKC-α activity. Mass spectrometry analysis and western blot analyses revealed a stimulation- and ILK-dependent phosphorylation of kindlin-3 upon activation. Our data thus show that ILK impacts kindlin-3-dependent conformational activation of LFA-1, thus contributing to an inflammatory response.
2020-07-20 | PXD017088 | Pride
Project description:Available evidence has suggested that integrin-linked kinase (ILK) underwent over-expression in ovarian cancer while specific gene silencing of ILK resulted in apoptosis of ovarian cancer cells. Here, potential mechanisms in which ILK induces cell apoptosis was explored from the perspective of microRNA (miRNA) expression.
2016-06-28 | GSE83721 | GEO
Project description:Available evidence has suggested that integrin-linked kinase (ILK) underwent over-expression in ovarian cancer while specific gene silencing of ILK resulted in apoptosis of ovarian cancer cells. Here, potential mechanisms in which ILK induces cell apoptosis was explored from the perspective of microRNA (miRNA) expression. Alteration in global miRNA expression profile was detected by miRNA microarray technique after ILK shRNA expression lentivirus was transfected into A2780 cells (n = 3). Additionally, the A2780 cells infected by scrambled shRNA lentivirus were treated as negtive control (n = 3).
2016-06-28 | E-GEOD-83721 | biostudies-arrayexpress
Project description:To identify receptors and pathways active in glioblastoma (GBM) stem like cells (GSCs), we generated and screened thousands of monoclonal antibodies (mAbs) for preferential binding to primary cultures enriched in GSCs. This led to the identification of the integrin alpha 7 (ITGA7) as a major laminin receptor in GSCs and in primary high-grade glioma specimens. Analyses of mRNA profiles in comprehensive datasets revealed that high ITGA7 expression was negatively correlated with survival of patients with both low- and high-grade glioma. In vitro and in vivo analyses demonstrated a key biological function of ITGA7 in growth and invasion of GSCs. In addition, we showed that targeting ITGA7 by RNAi or blocking mAbs impaired laminin-induced signaling and led to a significant delay of tumor engraftment and strong reduction in size and invasion. Our data underline the potential value of ITGA7 as glioma biomarker and therapeutic target.
2018-01-10 | PXD006069 | Pride
Project description:Neural crest defects lead to congenital heart disease involving outflow tract (OFT) malformation. Integrin-linked-Kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in neural crest cells (NCC), but its role in NCC and OFT morphogenesis remains unknown. We used microarrays to detail the global programme of gene expression underlying the morphogenesis of the cardiac neural crest and outflow tract. The outflow tract of control and ILK mutant mouse embryos at E10.5 were dissected and dissociated. Neural crest cells were FACS sorted and used for RNA extraction and hybridization on Affymetrix microarrays.
2012-10-01 | E-GEOD-41179 | biostudies-arrayexpress
Project description:Neural crest defects lead to congenital heart disease involving outflow tract (OFT) malformation. Integrin-linked-Kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in neural crest cells (NCC), but its role in NCC and OFT morphogenesis remains unknown. We used microarrays to detail the global programme of gene expression underlying the morphogenesis of the cardiac neural crest and outflow tract.
2012-10-01 | GSE41179 | GEO
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
Project description:Expression data from Integrin-linked kinase (ILK)-deficient epidermis
| PRJNA150729 | ENA