In another aspect, bile duct obstruction (BDO) has been reported to promote cholangiocarcinoma (CCA) progression, and evidence showed that elevated levels of conjugated bile acids activated ERK1/2 signaling pathway and were partially responsible for the cholangiocarcinoma cell growth and invasion, which could be significantly inhibited by S1PR2 antagonist [22]. This evidence concerns the gene MAPK3 and cholestasis.