Next, we investigated the ligand-independent activation of Notch signaling by analyzing mRNA expression levels of ADAM metallopeptidases, including ADAM9, -10, -12, and -17, which have been reported to regulate the Notch signaling pathway.37, 38, 39, 40, 41 Among these ADAMs, ADAM17 mRNA expression was significantly downregulated upon GPR50 knockdown in both HCC cell lines, HepG2 and SNU475 (Figure 5A). Here, GPR50 is linked to hepatocellular carcinoma.