Aberrant FoxM1B expression increases matrix metalloproteinase-2 transcription and enhances the invasion of glioma cells

作者: B Dai , S-H Kang , W Gong , M Liu , K D Aldape

DOI: 10.1038/SJ.ONC.1210443

关键词:

摘要: We recently showed that FoxM1 is overexpressed in human glioblastomas and forced FoxM1B expression anaplastic astrocytoma cells leads to the formation of highly invasive glioblastoma multiforme (GBM) nude mice. However, molecular mechanisms by which enhances glioma invasion are unknown. In this study, we found overexpression increased matrix metalloproteinase (MMP)-2 cells, whereas blockade suppressed MMP-2 expression. Transfection into directly activated promoter, inhibition FoxM1-siRNA its activation. identified a FoxM1-binding site promoter demonstrated protein bound it. Mutation significantly attenuated activity. Furthermore, invasiveness GBM cells. Inhibition specific inhibitor reversed phenotype overexpressing FoxM1. Finally, immunohistochemical analysis 45 specimens significant correlation between elevated Collectively, these findings provide evidence contributes progression enhancing gene transcription thus tumor-cell invasion.

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