Identification of therapeutic targets for glioblastoma by network analysis.

TitleIdentification of therapeutic targets for glioblastoma by network analysis.
Publication TypeJournal Article
Year of Publication2015
AuthorsFriedmann-Morvinski D, Bhargava V, Gupta S, Verma IM, Subramaniam S
JournalOncogene
Date Published2015 May 11
ISSN1476-5594
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.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.119.

DOI10.1038/onc.2015.119
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/25961929?dopt=Abstract
Alternate JournalOncogene
PubMed ID25961929