Egr-1 mediates extracellular matrix-driven transcription of membrane type 1 matrix metalloproteinase in endothelium

Matrix metalloproteinase activity is instrumental in processes of cellular invasion. The interstitial invasion of endothelial cells during angiogenesi s is accompanied by up-regulation of several matrix metalloproteinases, inc luding membrane type 1 matrix metalloproteinase (MT1-MMP), In this study, w e show that endothelial cells stimulated to undergo angiogenesis by a three -dimensional extracellular matrix environment increase production of the tr anscription factor Egr-1. Increased binding of Egr-1 to the MT1-MMP promote r correlates with enhanced transcriptional activity, whereas mutations in t he Egr-1 binding site abrogate the increased transcription of MT1-MMP in th e stimulated cells. These data identify Egr-1-mediated transcription of MT1 -MMP as a mechanism by which endothelial cells can initiate an invasive phe notype in response to an alteration in extracellular matrix environment, th us functionally associating MT1-MMP with a growing number of proteins known to be up-regulated by Egr-1 in response to tissue injury or mechanical str ess.