Protease-activated receptor 1 mediated altered Ca+2 signaling in gliomas

Abstract

Thrombin-activated receptor-1 induces angiogenesis, cell proliferation, and invasion in tumors. The protein-activated receptor-1 (PAR1) is a G-protein coupled receptor that can be catalyzed by blood-derived serine proteases. Though Protease-activated receptor 1 plays an imperative role in coagulation and hemostasis, recent studies have found that PAR1 activation also affects the central nervous system (CNS) in addition to the vasculature. The present study focused on examining the prevalence of PAR1 in two human gliomas cell lines, D54 and U87, as well as the downstream signaling pathway. PAR1 was significantly more expressed in D54 cells than in U87 cells. An increase in PAR1 activity caused an increase in ERK1/2 activity, along with increased migration and invasion. SCH79797 (antagonist) significantly reduced the migration and invasion of the glioma cell lines. These cell lines' migration and invasion upon activator and inhibitor stimulation were related to PAR1 expression. In cells, Ca + 2 concentration ([Ca + 2]i) is altered by PAR1. Thrombin and TFLLR both induced an increase in [Ca + 2]i that was inhibited by SCH79797 (PAR1 inhibitor). The study concludes that PAR1 signaling contributes to the progression of gliomas. PAR1 and its downstream signaling may act as potential therapeutic targets for the prevention of glioma formation.