Overexpression of 14-3-3 Modulates Cholangiocarcinoma Cell Survival by PI3K/Akt Signaling.

The protein 14-3-3 is involved in numerous cellular processes through its ability to bind phosphorylated serine/threonine residues. It is a key regulator of the cell cycle involving in G2 arrest by p53. Deregulation of 14-3-3 expression has been associated with a large variety of human cancers. However, its physiological function and therapeutic significance have rarely been investigated in cholangiocarcinoma. Using immunohistochemistry (IHC), we evaluated 14-3-3 expression in 65 human extrahepatic cholangiocarcinomas. As a result, we found that 14-3-3 is expressed in the tissue of 56 patients (86.2%), and its expression is positively correlated with tumor size, lymph node metastasis, and tumor stage. We also explored the significance of 14-3-3 and found that 14-3-3 exerts cell type-dependent effects on cell proliferation through PI3K/Akt signaling in both and xenograft models. These results suggest that 14-3-3 assumes a constitutive role in tumorigenesis rather than acting as a cell cycle regulator in cholangiocarcinoma, which makes 14-3-3 a new potential target for therapeutic intervention.