title: Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes.
abstract: Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA and beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer.
authors.affiliation: Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034, Russia; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034, Russia; Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178, USA. Electronic address: o.bazhenova@spbu.ru.
authors.forename: Olga
authors.initials: O
authors.lastname: Bajenova
authors.affiliation: Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Chaika
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Tolkunova
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Davydov-Sinitsyn
authors.affiliation: Boston Children׳s Hospital, Boston, MA 02115, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gapon
authors.affiliation: Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034, Russia.
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Brien
mesh_terms: D022005:Adherens Junctions / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D019073:HT29 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D051176:beta Catenin
keywords: Adherens junction; CEAR; Carcinoembryonic antigen; Colorectal carcinoma; E-cadherin; Metastasis; RNA binding protein; p120 catenin; α-catenin; β-catenin