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- W2080517825 abstract "ECRG2 is a novel gene that shows sequence similarity to KAZAL-type serine protease inhibitor. We have previously demonstrated that ECRG2 inhibits migration/invasion of lung cancer PG cells. However, the mechanism by which ECRG2 performs these activities is a compelling question. Urokinase-type plasmin activator (uPA) binding to uPAR induces migration/invasion through multiple interactors including integrins. In this study, we found that ECRG2 binds specifically to the kringle domain of uPA. Moreover, we demonstrated that ECRG2 forms a complex with uPA.uPAR, that such a complex modifies the dynamical association of uPAR with beta1 integrins, and that disruption inhibits Src/MAP (mitogen-activated protein) kinase pathway, resulting in suppression of cell migration/invasion in an in vitro Matrigel migration/invasion assay. Conversely, depletion of ECRG2 markedly enhanced the association of uPAR with beta1 integrins, elevated basal Src/MAP kinase activation, and stimulated HT1080, MDA-MB-231, and MCF-7 cell migration/invasion. Together, our results provide evidence that ECRG2 is involved in the regulation of migration/invasion through uPA/uPAR/beta1 integrins/Src/MAP kinase pathway and may represent a novel therapeutic target for cancer." @default.
- W2080517825 created "2016-06-24" @default.
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- W2080517825 date "2009-11-01" @default.
- W2080517825 modified "2023-09-30" @default.
- W2080517825 title "ECRG2 Regulates Cell Migration/Invasion through Urokinase-type Plasmin Activator Receptor (uPAR)/β1 Integrin Pathway" @default.
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- W2080517825 doi "https://doi.org/10.1074/jbc.m109.011213" @default.
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