RRC ID |
34787
|
著者 |
Kobayashi K, Takahashi H, Inoue A, Harada H, Toshimori S, Kobayashi Y, Goto K, Sugimoto K, Yano H, Ohnishi T, Tanaka J.
|
タイトル |
Oct-3/4 promotes migration and invasion of glioblastoma cells.
|
ジャーナル |
J Cell Biochem
|
Abstract |
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.
|
巻・号 |
113(2)
|
ページ |
508-17
|
公開日 |
2012-2-1
|
DOI |
10.1002/jcb.23374
|
PMID |
21938739
|
MeSH |
Actin Cytoskeleton / metabolism
Animals
Brain / pathology
Brain Neoplasms / metabolism
Brain Neoplasms / pathology*
Cell Movement*
Focal Adhesions / metabolism
Gene Expression
Gene Expression Regulation, Neoplastic
Glioblastoma / metabolism
Glioblastoma / pathology*
Humans
Integrins / genetics
Integrins / metabolism
Matrix Metalloproteinase 13 / genetics
Matrix Metalloproteinase 13 / metabolism
Neoplasm Invasiveness
Octamer Transcription Factor-3 / genetics
Octamer Transcription Factor-3 / metabolism*
Rats
Rats, Wistar
Tissue Culture Techniques
Tumor Cells, Cultured
Up-Regulation
|
IF |
4.237
|
引用数 |
28
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
リソース情報 |
遺伝子材料 |
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393) |