Transcriptomics

Dataset Information

3

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. 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: Wei Zhang   Sarah M Dunlap  Matti J Annala  Niek Hugen  Chua Yingxuan  Matti Annala  Yuexin Liu  Matti Nykter  Kristen M Holmes  Lynette M Moore  Gregory N Fuller  Kenneth Hess  Limei Hu  David Cogdell 

PROVIDER: E-GEOD-35467 | ArrayExpress | 2012-02-02

SECONDARY ACCESSION(S): GSE35467PRJNA152343

REPOSITORIES: GEO, ArrayExpress

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