Identification of therapeutic targets for glioblastoma by network analysis

D. Friedmann-Morvinski, V. Bhargava, S. Gupta, I. M. Verma*, S. Subramaniam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Glioblastoma can originate from terminally differentiated astrocytes and neurons, which can dedifferentiate to a stem cell-like state upon transformation. In this study, we confirmed that transformed dedifferentiated astrocytes and neurons acquired a stem/progenitor cell state, although they still retained gene expression memory from their parental cell. Transcriptional network analysis on these cells identified upregulated genes in three main pathways: Wnt signaling, cell cycle and focal adhesion with the gene Spp1, also known as osteopontin (OPN) serving as a key common node connecting these three pathways. Inhibition of OPN blocked the formation of neurospheres, affected the proliferative capacity of transformed neurons and reduced the expression levels of neural stem cell markers. Specific inhibition of OPN in both murine and human glioma tumors prolonged mice survival. We conclude that OPN is an important player in dedifferentiation of cells during tumor formation, hence its inhibition can be a therapeutic target for glioblastoma.

Original languageEnglish
Pages (from-to)608-620
Number of pages13
JournalOncogene
Volume35
Issue number5
DOIs
StatePublished - 4 Feb 2016

Funding

FundersFunder number
Cancer CenterP30 CA014195-38
National Science FoundationSTC-0939370, DBI-0835541
National Institutes of Health
National Heart, Lung, and Blood InstituteHL087375, HL106579, HL108735
National Cancer InstituteP30CA023100
California Institute for Regenerative MedicineTG2-01154, T1-00003
Leona M. and Harry B. Helmsley Charitable Trust2012-PG-MED002

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