title: Restoration of E-cadherin-based cell-cell adhesion by overexpression of nectin in HSC-39 cells, a human signet ring cell gastric cancer cell line.
abstract: Nectin is an immunoglobulin-like adhesion molecule that comprises a family consisting of four members, nectin-1, -2, -3, and -4. Nectin is associated with the actin cytoskeleton through afadin, a nectin- and actin filament-binding protein. The nectin-afadin and cadherin-catenin systems are associated with each other and cooperatively form cell-cell adherens junctions in intact epithelial cells. HSC-39 cells, a human signet ring cell gastric cancer cell line, express E-cadherin but do not form cell-cell adhesion. The beta-catenin gene has been shown to be truncated at the N-terminal region including the alpha-catenin-binding domain in HSC-39 cells, but overexpression of normal beta-catenin failed to form cell-cell adhesion. HSC-39 cells expressed nectin-1, -2, and afadin, but not nectin-3. Overexpression of nectin-3 or -2 formed cell-cell adhesion and accumulation of E-cadherin, but not actin filaments, at the cell-cell adhesion sites. Overexpression of a truncated form of nectin-2 incapable of interacting with afadin failed to form cell-cell adhesion. However, the nectin-formed cell-cell adhesion was not so strong as that observed in epithelial cells, such as CaCo-2 cells. Co-expression of nectin-2 and normal beta-catenin did not form strong cell-cell adhesion. These results suggest that an unidentified mechanism, by which nectin and E-cadherin form the actin cytoskeleton-associated adherens junctions to form strong cell-cell adhesion, is impaired in HSC-39 cells.
authors.affiliation: Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
authors.forename: Ying-Feng
authors.initials: YF
authors.lastname: Peng
authors.forename: Kenji
authors.initials: K
authors.lastname: Mandai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Wataru
authors.initials: W
authors.lastname: Ikeda
authors.forename: Masanori
authors.initials: M
authors.lastname: Asada
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Momose
authors.forename: Sayumi
authors.initials: S
authors.lastname: Shibamoto
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiozaki
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeichi
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Takai
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000502:physiology*; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D017931:DNA Primers; D006801:Humans; D008856:Microscopy, Fluorescence; D000075983:Nectins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D017931:DNA Primers; C000619010:NECTIN1 protein, human; C000619014:NECTIN3 protein, human; D000075983:Nectins