» Articles » PMID: 30241478

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

Overview
Publisher Biomed Central
Date 2018 Sep 23
PMID 30241478
Citations 4
Authors
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.

Citing Articles

Elevated expression of gene in tumors is a poor prognostic biomarker for patients with bladder cancer.

Franco L, Arunachalam S, Chauhan A, Kareff S, Hallenbeck P Front Mol Biosci. 2025; 11:1520223.

PMID: 39917181 PMC: 11798775. DOI: 10.3389/fmolb.2024.1520223.


GLIPR1 Protects Against Cigarette Smoke-Induced Airway Inflammation via PLAU/EGFR Signaling.

Peng W, Wu Y, Zhang G, Zhu W, Chang M, Rouzi A Int J Chron Obstruct Pulmon Dis. 2021; 16:2817-2832.

PMID: 34675506 PMC: 8517531. DOI: 10.2147/COPD.S328313.


TEM8 marks neovasculogenic tumor-initiating cells in triple-negative breast cancer.

Xu J, Yang X, Deng Q, Yang C, Wang D, Jiang G Nat Commun. 2021; 12(1):4413.

PMID: 34285210 PMC: 8292527. DOI: 10.1038/s41467-021-24703-7.


Latest therapeutic target for gastric cancer: Anthrax toxin receptor 1.

Sun K, Lv H, Chen B, Nie C, Zhao J, Chen X World J Gastrointest Oncol. 2021; 13(4):216-222.

PMID: 33889273 PMC: 8040068. DOI: 10.4251/wjgo.v13.i4.216.


Anthrax Edema and Lethal Toxins Differentially Target Human Lung and Blood Phagocytes.

Patel V, Booth J, Dozmorov M, Brown B, Metcalf J Toxins (Basel). 2020; 12(7).

PMID: 32698436 PMC: 7405021. DOI: 10.3390/toxins12070464.

References
1.
Holash J, Davis S, Papadopoulos N, Croll S, Ho L, Russell M . VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A. 2002; 99(17):11393-8. PMC: 123267. DOI: 10.1073/pnas.172398299. View

2.
Jiang Y, Pannell R, Liu J, Gurewich V . Evidence for a novel binding protein to urokinase-type plasminogen activator in platelet membranes. Blood. 1996; 87(7):2775-81. View

3.
Gu J, Faundez V, Werner E . Endosomal recycling regulates Anthrax Toxin Receptor 1/Tumor Endothelial Marker 8-dependent cell spreading. Exp Cell Res. 2010; 316(12):1946-57. PMC: 2886593. DOI: 10.1016/j.yexcr.2010.03.026. View

4.
Abrami L, Bischofberger M, Kunz B, Groux R, van der Goot F . Endocytosis of the anthrax toxin is mediated by clathrin, actin and unconventional adaptors. PLoS Pathog. 2010; 6(3):e1000792. PMC: 2832758. DOI: 10.1371/journal.ppat.1000792. View

5.
Carson-Walter E, Watkins D, Nanda A, Vogelstein B, Kinzler K, St Croix B . Cell surface tumor endothelial markers are conserved in mice and humans. Cancer Res. 2001; 61(18):6649-55. View