CEACAM6 induces epithelial-mesenchymal transition and mediates invasion and metastasis in pancreatic cancer

Int J Oncol. 2013 Sep;43(3):877-85. doi: 10.3892/ijo.2013.2015. Epub 2013 Jul 12.

Abstract

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition / genetics*
  • GPI-Linked Proteins / biosynthesis
  • GPI-Linked Proteins / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • RNA, Small Interfering / genetics

Substances

  • Antigens, CD
  • CEACAM6 protein, human
  • Cell Adhesion Molecules
  • GPI-Linked Proteins
  • MIRN29a microRNA, human
  • MicroRNAs
  • RNA, Small Interfering