Furthermore, the iNOS-dependent COX-2 activation through the p38 MAPK/JNK axis, leads, in CCA, to the generation of high amounts of prostaglandin E2 (PGE2), which in turn, by binding its specific receptor EP1, can induce a tumorigenic effect by enhancing neoplastic cell proliferation and invasiveness. This evidence concerns the gene MAPK8 and cholangiocarcinoma.