Insulin-like growth factor-binding protein 2-driven glioma progression is prevented by blocking a clinically significant integrin, integrin-linked kinase, and NF-κB network

Kristen M. Holmes, Matti Annala, Corrine Y.X. Chua, Sarah M. Dunlap, Yuexin Liu, Niek Hugen, Lynette M. Moore, David Cogdell, Limei Hu, Matti Nykter, Kenneth Hess, Gregory N. Fuller, Wei Zhang

Research output: Contribution to journalArticle

78 Scopus citations

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 gliomawith validation in glial cells and the replicationcompetent ASLV long terminal repeatwith 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 downstream 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.

Original languageEnglish (US)
Pages (from-to)3475-3480
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number9
DOIs
StatePublished - Feb 28 2012

ASJC Scopus subject areas

  • General

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