Abstract
The immunoglobulin superfamily member carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is overexpressed in a wide variety of human cancer types, and is associated with tumor invasion and migration. The aim of the present study was to determine the role of CEACAM6 in cholangiocarcinoma (CCA) invasion and migration in vitro. The results showed that CEACAM6 was highly expressed in CCA tissues, and that the expression level of CEACAM6 was negatively associated with the degree of differentiation of CCA. Silencing CEACAM6 inhibited cell viability, invasion and migration but promoted cell apoptosis in a human CCA cell line (RBE). In addition, CEACAM6 knockdown decreased the expression of an antiapoptotic protein (Bcl-2), an interstitial cell marker (N-cadherin), extracellular matrix proteins (MMP-2 and MMP-9), a transcription factor helix protein (Twist-related protein 1), an intermediate tumor cell scaffold marker (vimentin), a protein involved in tumor nutrient vascular formation (VEGFA) and a tumorigenesis factor (intercellular cell adhesion molecule-1), but increased the expression of pro-apoptotic proteins (Bax, and cleaved caspases-3, -8 and -9) and an epithelial cell marker protein (E-cadherin). Furthermore, CEACAM6-small interfering RNA reduced the expression of the SRC/PI3K/AKT signaling transduction pathway. Taken together, these results suggested that CEACAM6 may be an epithelial-mesenchymal transition biomarker and a potential therapeutic target in human CCA.