4.6 Article

Oct-3/4 promotes migration and invasion of glioblastoma cells

Journal

JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 113, Issue 2, Pages 508-517

Publisher

WILEY-BLACKWELL
DOI: 10.1002/jcb.23374

Keywords

GLIOBLASTOMA; Oct-3; 4; INVASION; INTEGRIN; MATRIX METALLOPROTEINASE

Funding

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [21791366, 23592129]
  2. Grants-in-Aid for Scientific Research [21791366, 23592129, 22390037, 23592130, 23659688] Funding Source: KAKEN

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As a result of increased glioblastoma migration and invasion into normal brain parenchyma, treatment of local tumor recurrence following initial treatment in glioblastoma patients remains challenging. Recent studies have demonstrated increased Oct-3/4 expression, a self-renewal regulator in stem cells, in glioblastomas. However, little is known regarding the influence of Oct-3/4 in glioblastoma cell invasiveness. The present study established Oct-3/4-overexpressing glioblastoma cells, which were prepared from human glioblastoma patients, to assess migration, invasion, and mRNA expression profiles of integrins and matrix metalloproteinases (MMPs). Compared with control cells, Oct-3/4 expressing-glioblastoma cells exhibited increased migration and invasion in wound healing and Matrigel invasion assays. Oct-3/4 overexpression resulted in upregulated FAK and c-Src expression, which mediate integrin signals. Vinculin accumulated along the leading edges of Oct-3/4 expressing-glioblastoma cells and associated with membrane ruffles during cell migration. Oct-3/4 expressing-cells exhibited increased MMP-13 mRNA expression and MMP-13 knockdown by shRNA suppressed cell invasion into Matrigel and organotypic brain slices. These results suggested that Oct-3/4 enhanced degradation of surrounding extracellular matrix by increasing MMP-13 expression and altering integrin signaling. Therefore, Oct-3/4 might contribute to tumor promoting activity in glioblastomas. J. Cell. Biochem. 113: 508517, 2012. (C) 2011 Wiley Periodicals, Inc.

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