TEM8 Functions As a Receptor for UPA and Mediates UPA-stimulated EGFR Phosphorylation

Overview

Journal Cell Commun Signal

Publisher Biomed Central

Specialties Biochemistry
Cell Biology

Date 2018 Sep 23

PMID 30241478

Citations 4

Authors

Lian-Cheng Zhang

Yong Shao

Li-Hua Gao

Jin Liu

Yong-Yi Xi

Yin Xu

ChuTse Wu

Wei Chen

Hui-Peng Chen

You-Liang Wang

Hai-Feng Duan

Xian-Wen Hu

Affiliations

Soon will be listed here.

Abstract

Background: 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.

Results: 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.

Conclusions: 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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