title: An alternatively spliced cadherin-11 enhances human breast cancer cell invasion.
abstract: Although reduced levels of the epithelial cell adhesion molecule E-cadherin are often associated with poorly differentiated breast cancers, recent studies show that expression of other cadherins such as N-cadherin, P-cadherin, and the mesenchymal cadherin-11 is actually elevated in invasive breast cancers and cell lines. Cadherin-11 is unique among cadherins in that it exists as two alternatively spliced forms that are expressed together in the same cell. We now show that expression of wild-type cadherin-11, with or without coexpression of the COOH-terminal truncated splice variant, promotes epithelial differentiation of the cadherin-negative SKBR3 cell line. Exogenous wild-type cadherin-11 association with and membrane recruitment of beta-catenin and p120 are unaffected by coexpression of the truncated variant. Cadherin-11-expressing cells exhibit modest changes in cell proliferation and no change in anchorage-independent growth. However, coexpression of wild-type cadherin-11 and the splice variant promotes a dramatic increase in the ability of SKBR3 cells and E-cadherin-positive MCF7 cells to traverse Matrigel-coated filters. Biochemical studies indicate that the truncated variant may be secreted from the cell and/or enter a detergent-insoluble compartment. These data suggest that the presence of the cadherin-11 splice variant promotes invasion of cadherin-11-positive breast cancer cells.
authors.affiliation: Lombardi Cancer Research Center and Department of Oncology, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Feltes
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Orest
authors.initials: O
authors.lastname: Blaschuk
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Byers
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism / Q000502:physiology; D017398:Alternative Splicing; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000918:Antibody Specificity; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D015820:Cadherins; C086960:osteoblast cadherin