Abstract

Pancreatic cancer is a disease with anextremely poor prognosis. The acquisition of invasion properties in pancreaticcancer is accompanied by the process of epithelial-mesenchymal transition (EMT).Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is emergingas an important determinant of the malignant phenotype in a range of cancers,including pancreatic cancer. Therefore, the aim of this study was to evaluatethe potential involvement of CEACAM6 in the invasion and metastasis ofpancreatic cancer cells via EMT regulation. The results of our study showed apositive association between CEACAM6 expression and poor prognosis ofpancreatic cancer, differentiation and lymph node metastasis. Elevated levelsof CEACAM6 in pancreatic cancer cells promoted EMT, migration and invasion invitro and metastasis in animal models, whereas shRNA-mediated CEACAM6 knockdownhad the opposite effect. Furthermore, we demonstrated that miR-29a/b/c specificfor CEACAM6 could regulate its expression at the post-transcriptional level.Collectively, our findings identified CEACAM6, which is regulated bymiR-29a/b/c, as an important positive regulator of EMT in pancreatic canceroffering an explanation for how elevated levels of CEACAM6 are likely tocontribute to the highly metastatic phenotype of pancreatic cancer.