Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Carcinoembryonic antigen promotes metastasis via disruption of E-cadherin adherens junction complexes. (#96)

Olga Bajenova 1 , Nina Chaika 2 , Peter Thomas 2
  1. Department of Genetics and Selection, St. Petersburg State University, St Petersburg, Russia
  2. Department of Surgery and Biomedical Sciences, Creighton University, Omaha, USA

Carcinoembryonic antigen (CEA) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. In this study we investigated the mechanism of CEA tumorigenesis, particularly the effect of CEA production on E-cadherin adherens junction protein complexes. As a model we used CEA-producing and non-producing MIP101 colorectal carcinoma cell lines. By immunoprecipitation we discovered the novel interactions between CEA and -catenin in the CEA excreting cells. No direct interaction has been detected between E-cadherin and CEA and no downregulation of neither -catenin nor E-cadherin in the CEA overexpressing cells. In addition, the functional interactions between E-cadherin and its binding protein- -catenin as well as between cateninand catenin have been impared in the CEA-producing cell lines. β-catenin is also a key factor in the Wnt signaling pathway that has essential functions in the regulation of cell growth and differentiation. Aberrant β-catenin signaling has been linked to the various disease pathologies, including an important role in metastasis. We have previously identified and cloned a novel CEA-binding protein (CEAR) from the liver macrophages, Kupffer cells. It has been shown that CEA-CEAR binding produces an inflammatory response in the liver by altering the microenvironment such that implantation and survival of tumor cells increases. This study also identified novel interactions of CEAR with α-catenin that may interfere with the  catenin and its signaling pathways. Our findings indicate that the CEA production in tumors contributes to EMT and metastatic dissemination by interfering with the function of E-cadherin adherens junction complexes. This may explain the link between the elevated levels of CEA and an increase in the soluble E-cadherin during the progression of colorectal cancer. This work has been supported by The Russian Foundation for Fundamental Research and by the Health and Future Foundation of Creighton University.