However, the mutations of TGFβ receptor and the alterations of intracellular signaling mediators (e.g., Smad4) together with the intracellular overexpression of cyclin D1 [25, 26] in CC cells induce a resistance to the inhibitory effect of TGFβ cells [27]. The gene discussed is TGFB1; the disease is cholangiocarcinoma.