In summary, 14-3-3ζ binds to aPKC-ι and activate aPKC-ι through phosphorylation, and activation of aPKC-ι lead to the suppression of GSK-3β through phosphorylation of Ser 9, and furthermore, inhibition of GSK-3β results in the upregulation of Snail and downregulation of E-cadherin, and promotes the EMT ultimately in CCA cells (Figure 7D). This evidence concerns the gene CDH1 and cholangiocarcinoma.