Urokinase is a negative modulator of Egf-dependent proliferation and motility in the two XXXX cell lines MCF-7 and MDA-MB-231.

@entity0 @entity10431 @entity470 @entity5 @entity3963 @entity584 @entity1366 @entity2290
UNASSIGNED: The @entity470 ( @entity470 ) is involved in the regulation of various cellular processes and dysregulation of its signalling plays a critical role in the etiology of a variety of @entity5 like @entity0 . At the same time, elevated levels of urokinase ( @entity2290 ), its receptor @entity10431 , and other components of the plasminogen activation system are found to be correlated with a poor prognosis in @entity0 . Interestingly, @entity470 appears to participate in transducing the signal generated upon binding of @entity2290 to @entity10431 . However, whether @entity2290 signalling would thereby interfere with ligand-driven @entity470 signalling was not described before. Therefore, it was the aim of the present study to investigate the combined effects of @entity2290 and EGF in the low invasive and high invasive @entity0 cell lines MCF-7 and MDA-MB-231, respectively. Simultaneous exposure of cells to both signals negatively affected @entity1366 and @entity584 activation whereas positive effects on @entity3963 and Src kinase phosphorylation were noted in both cell lines. Furthermore, @entity2290 attenuated the mitogenic effect of EGF on cellular proliferation, invasion and motility in both MCF-7 and MDA-MB-231 cells. Experiments with the @entity2290 amino terminal fragment (ATF) revealed that the negative effects of @entity2290 were independent from its protease activity. Together, these data suggest that enhanced levels of @entity2290 in @entity0 modulate the mitogenic effects of EGF and thus, this knowledge may help to better understand @entity0 pathogenesis as well as to develop new therapeutic options.    2015 Wiley Periodicals, Inc.
