JAG1 and cholangiocarcinoma: Che et al. found that JAG1 is generally up-regulated in human iCCA samples compared with non-neoplastic livers, and inhibiting JAG1 can increase the apoptosis of human iCCA cell lines.125 Importantly, JAG1 is a crucial upstream inducer of Notch signaling in human and mouse iCCA.125 The synergistic overexpression of JAG1 and activated AKT signaling promotes the occurrence of liver cancer.125 In summary, activated Notch signaling is identified as a common carcinogenic event in human CCA.