biostudies-literatureZhang LCthe National Science and Technology Major Projectthe National Science Foundation of China62https://www.ebi.ac.uk/biostudies/studies/S-EPMC6151050biostudies-literatureUnknown16(1)<h4>Background</h4>TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown.<h4>Results</h4>Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation weCell communication and signaling : CCSTEM8 functions as a receptor for uPA and mediates uPA-stimulated EGFR phosphorylation.PMC61510502012ZX09102-3012009ZX09103-626309059230973670Chen HPWang YLLiu JShao YGao LHXi YYWu CChen WDuan HFZhang LCHu XWXu YfalseTEM8 functions as a receptor for uPA and mediates uPA-stimulated EGFR phosphorylation.<h4>Background</h4>TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown.<h4>Results</h4>Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation we2018-01-01T00:00:00Z2018 Sep2026-06-08T05:59:20.101Z2026-06-08T03:14:14.792ZS-EPMC61510503024147810.1186/s12964-018-0272-8