Protease-activated receptor-1 impedes prostate and intestinal tumor progression in mice.

Journal of Thrombosis and Haemostasis : JTH
G N AdamsJ S Palumbo

Abstract

Essentials Protease activated receptor-1 (PAR-1) has been proposed to drive cancer progression. Surprisingly, PAR-1 deletion accelerated tumor progression in two distinct experimental settings. PAR-1 deletion was shown to limit the apoptosis of transformed epithelial cells. Thrombin- and activated protein C-mediated PAR-1 activation have unique effects on tumor cell biology. SUMMARY: Background Multiple studies have implicated protease-activated receptor-1 (PAR-1), a G-protein-coupled receptor activated by proteolytic cleavage of its N-terminus, as one target coupling thrombin-mediated proteolysis to tumor progression. Objective To analyze the role of PAR-1 in the setting of two distinct spontaneously developing tumor models in mice. Methods We interbred PAR-1-deficient mice with Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, which spontaneously develop prostate tumors, and adenomatous polyposis coli Min (APCM in/+ ) mice, which spontaneously develop intestinal adenomas. Results Analyses of TRAMP mice with advanced disease (30 weeks) revealed that PAR-1 deficiency resulted in significantly larger and more aggressive prostate tumors. Prostates collected at an earlier time point (12 weeks of age) revealed that PAR-...Continue Reading

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Citations

Nov 10, 2018·Journal of Thrombosis and Haemostasis : JTH·C A SpekM F Bijlsma
Aug 9, 2019·Journal of Thrombosis and Haemostasis : JTH·Anaum MaqsoodNigel Mackman
Sep 9, 2019·The FEBS Journal·Giulia PontarolloChristoph Reinhardt
Aug 19, 2020·Cellular Oncology (Dordrecht)·Cansu TekinC Arnold Spek
Nov 12, 2019·Frontiers in Endocrinology·Morgane SébertAudrey Ferrand
Oct 17, 2020·Journal of Thrombosis and Haemostasis : JTH·Patrick G SchweickertStephen F Konieczny
Jun 3, 2021·International Journal of Molecular Sciences·Aditi Kothari, Matthew J Flick
Jun 22, 2021·Seminars in Thrombosis and Hemostasis·Julie Brogaard Larsen, Anne-Mette Hvas
Jul 1, 2021·Journal of Thrombosis and Haemostasis : JTH·Bal Krishan SharmaJoseph S Palumbo

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