Girdin maintains the stemness of glioblastoma stem cells

A. Natsume, T. Kato, S. Kinjo, A. Enomoto, H. Toda, S. Shimato, F. Ohka, K. Motomura, Y. Kondo, T. Miyata, M. Takahashi, T. Wakabayashi

研究成果: Article査読

62 被引用数 (Scopus)

抄録

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/ΒIII Tubulin. Our results reveal that Girdin is required for GBM-initiating stem cells to sustain the stemness and invasive properties.

本文言語English
ページ(範囲)2715-2724
ページ数10
ジャーナルOncogene
31
22
DOI
出版ステータスPublished - 31-05-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 遺伝学
  • 癌研究

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