TEM8 functions as a receptor for uPA and mediates uPA-stimulated EGFR phosphorylation

Cell Communication and Signaling : CCS
Lian-Cheng ZhangXian-Wen Hu

Abstract

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. 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 were found co-located on frozen cancer tissue sections. Taken together, our data provide evidence that TEM8 is a novel receptor for uPA, which may play a significant role in the regulation of tumor growth and metastasis.

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Citations

Apr 24, 2021·World Journal of Gastrointestinal Oncology·Ke-Ran SunXiao-Bing Chen
Jul 22, 2021·Nature Communications·Jiahui XuSuling Liu

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Methods Mentioned

BETA
ELISA
FRET
surface
biosensor
chip
confocal microscopy
antibody Array
Antibody Arrays
immunoprecipitation
transfection

Software Mentioned

Gene Pix pro
BIA evaluation
MASCOT

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