NOTCH1 and cholangiocarcinoma: Moreover, ectopic expression of the human NOTCH1 ICD, in combination with the expression of constitutively active myristoylated AKT (myrAKT), induces the formation of intrahepatic cholangiocarcinoma in mice in the absence of underlying disease (Fan et al., 2012) by causing hepatocytes to undergo hepatocyte-to-cholangiocyte conversion (Sekiya and Suzuki, 2012) (Fig. 4B).