title: Oct-3/4 promotes migration and invasion of glioblastoma cells.
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.
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Inoue
authors.forename: Hironobu
authors.initials: H
authors.lastname: Harada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toshimori
authors.forename: Yukako
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Goto
authors.forename: Kana
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Yano
authors.forename: Takanori
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D022001:Focal Adhesions / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D046509:Tissue Culture Techniques; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D016023:Integrins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13