CD81 and hepatocellular carcinoma: For example, hepatitis C virus (HCV) NS4B impairs Hippo signaling to activate YAP, promoting the migration and invasion of hepatoma cells by activating the downstream PI3K/AKT pathway (44, 45), while the HCV E2 protein enhances the activity of Hippo to suppress YAP activation by mimicking glypican (GPC)-3 binding to CD81, an upstream regulator of the Hippo pathway (46).