Here in ICC cells, ERK1/2 activation attenuated TGF-β anti-proliferative activity; however, the level of phospho-Smad was marginally affected by U0126 suggesting the role of Smad-independent pathways, such as AP-1 activation, to support cell proliferation in the presence of TGF-β. This evidence concerns the gene TGFB1 and intrahepatic cholangiocarcinoma.