Autocrine Proteinase-Activated Receptor (PAR) signaling in PC3 prostate cancer cells

In this study, we examined the androgen independent human prostatic cancer cell line PC3 and find functional expression of PAR1 and PAR2 but not PAR4. Using genetically encoded PAR cleavage biosensors, we show that PC3 cells secrete proteolytic enzymes that cleave PARs and trigger autocrine signaling. CRISPR/Cas9 targeting of PAR1 and PAR2 combined with microarray analysis revealed genes that are regulated through this autocrine signaling mechanism. We find several genes that are known PCa prognostic factors or biomarker to be differentially expressed in the PAR1-KO and PAR2-KO PC3 cells. We further examined PAR1 and PAR2 regulation of PCa cell proliferation and migration and find that absence of PAR1 promotes PC3 cell migration and suppresses cell proliferation while PAR2 deficiency showed opposite effects. Overall, these results demonstrate that autocrine signaling through PARs is an important regulator of PCa cell function.PMID:37273236 | DOI:10.1152/ajpcell.00382.2022
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Source Type: research