Journal
ONCOGENE
Volume 31, Issue 22, Pages 2715-2724Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.466
Keywords
Girdin; glioblastoma; cancer stem cells; migration; stemness
Funding
- Grants-in-Aid for Scientific Research [22117005, 23791592] Funding Source: KAKEN
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Glioblastomas (GBMs) are the most common and aggressive type of brain tumor. GBMs usually show hyperactivation of the PI3K-Akt pathway, a pro-tumorigenic signaling cascade that contributes to pathogenesis. Girdin, an actin-binding protein identified as a novel substrate of Akt, regulates the sprouting of axons and the migration of neural progenitor cells during early postnatal-stage neurogenesis in the hippocampus. Here, we show that Girdin is highly expressed in human glioblastoma (GBM). Stable Girdin knockdown in isolated GBM stem cells resulted in decreased expression of stem cell markers, including CD133, induced multilineage neural differentiation, and inhibited in vitro cell motility, ex vivo invasion, sphere-forming capacity and in vivo tumor formation. Furthermore, exogenous expression of the Akt-binding domain of Girdin, which competitively inhibits its Akt-mediated phosphorylation, diminished the expression of stem cell markers, SOX2 and nestin, and migration on the brain slice and induced the expression of neural differentiation markers glial fibrillary acidic protein/beta III Tubulin. Our results reveal that Girdin is required for GBM-initiating stem cells to sustain the stemness and invasive properties. Oncogene (2012) 31, 2715-2724; doi: 10.1038/onc.2011.466; published online 24 October 2011
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