Overexpression of 14-3-3σ Modulates Cholangiocarcinoma Cell Survival by PI3KAkt Signaling

Abstract EN

The protein 14-3-3σ 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 14-3-3σ 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 14-3-3σ expression in 65 human extrahepatic cholangiocarcinomas.

As a result, we found that 14-3-3σ 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 14-3-3σ and found that 14-3-3σ exerts cell type-dependent effects on cell proliferation through PI3K/Akt signaling in both in vitro and in vivo xenograft models.

These results suggest that 14-3-3σ assumes a constitutive role in tumorigenesis rather than acting as a cell cycle regulator in cholangiocarcinoma, which makes 14-3-3σ a new potential target for therapeutic intervention.