Three mechanisms may underlie this effect: (1) LPA binding to G-protein-coupled receptors (LPARs), which triggers EFA6 recruiting to GTP-Ga12, thus activating downstream Arf6 51; (2) Arf6 activation coordinates Rac1, Cdc42, and RhoA to initiate macropinosome formation 18, 52, and (3) LPAR1, 3, and 6 are highly expressed in HCC 53. Here, LPAR1 is linked to hepatocellular carcinoma.