Recently, we discovered another mode through which PAR2 may enhance tumorigenesis: crosstalk with transforming growth factor-β (TGF-β) signaling to promote TGF-β1-induced cell migration/invasion and invasion-associated gene expression in ductal pancreatic adenocarcinoma (PDAC) cells.
Additional experiments in PDAC cells revealed that PAR2 and TGF-<i>β</i>1 synergy may involve TGF-<i>β</i>1 induction of enzymes that cause autocrine cleavage/activation of PAR2, possibly through a biased signaling function.
Therapeutically targeting PAR2 may thus be a promising approach in preventing TGF-β-dependent driven metastatic dissemination in PDAC and possibly other stroma-rich tumour types.