Transcriptional Regulation of the Urokinase Receptor (u-PAR) – A Central Molecule of Invasion and Metastasis

Urokinase-Type Plasminogen Activator Deficiency Promotes Neoplasmatogenesis in the Colon of Mice

“…Our findings regarding Treg are interesting, given the debated role of this immune-suppressive subset of lymphocytes in carcinogenesis [53], [65], [66]. Indeed, the roles of Treg in cancer appear paradoxical.…”

Effect of vasoconstrictor coupling factor 6 on gene expression profile in human vascular endothelial cells: enhanced release of asymmetric dimethylarginine

“…The binding of estradiol to estrogen receptor b leads to a decrease in occludin production at tight junctions and thereby promotes cell infiltration and the vascular spread of the cells [14]. Activation of u-PAR induces degradation of fibronectin and collagen, leading to enhancement of cell filtration and vascular remodeling [15].…”

“…As shown in Table 1, the genes with increased expression after 24-h exposure to coupling factor 6 at 10 À7 mol/l included endothelin-2 relating to vasoconstriction, neuregulin-1 and relaxin 1 relating to congestive heart failure, and protein arginine methyltransferase (PRMT-1) relating to ADMA synthesis. Although the increase was not significant, the genes of urokinase type plasminogen activator receptor (u-PAR) and estrogen receptor b, relating to vascular inflammation and the spread of the cells, tended to be increased [14,15]. In contrast, there were no negatively regulated genes.…”

Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors

“…Our present work suggests that the suppression of migration and invasion by Pdcd4 is, at least in part, brought about by a downregulation of the urokinase receptor (u-PAR), which, together with its binding enzyme u-PA and its specific inhibitor PAI-1, has been well established as a proteolytic system promoting invasion/metastasis and a poor clinical prognosis in diverse cancers (Duffy, 1987;Blasi, 1993;Heiss et al, 1996;Muehlenweg et al, 2001). Although it is well established that u-PAR is regulated by many growth factors, oncogenes (Boyd and Brattain, 1989;Lengyel et al, 1996;Allgayer et al, 1999a-c) and signaling cascades promoting proliferation/progression (AguirreGhiso et al, 2001;Aguirre-Ghiso et al, 2003;Ahmed et al, 2003), no tumor suppressor gene has been identified so far regulating u-PAR gene expression (Fuchs and Allgayer, 2003). According to previous studies, the regulation of u-PAR gene expression has largely been observed at the transcriptional level (Wang et al, 1994;Wagner et al, 1995;Lengyel et al, 1996), and correspondingly, we showed that Pdcd4 reduces u-PAR promoter activity, and that siPdcd4 induces u-PAR mRNA, in our cell lines studied, suggesting transcriptional regulation.…”