title: Binding of the sialic acid-binding lectin, Siglec-9, to the membrane mucin, MUC1, induces recruitment of β-catenin and subsequent cell growth.
abstract: Because MUC1 carries a variety of sialoglycans that are possibly recognized by the siglec family, we examined MUC1-binding siglecs and found that Siglec-9 prominently bound to MUC1. An immunochemical study showed that Siglec-9-positive immune cells were associated with MUC1-positive cells in human colon, pancreas, and breast tumor tissues. We investigated whether or not this interaction has any functional implications for MUC1-expressing cells. When mouse 3T3 fibroblast cells and a human colon cancer cell line, HCT116, stably transfected with MUC1cDNA were ligated with recombinant soluble Siglec-9, β-catenin was recruited to the MUC1 C-terminal domain, which was enhanced on stimulation with soluble Siglec-9 in dose- and time-dependent manners. A co-culture model of MUC1-expressing cells and Siglec-9-expressing cells mimicking the interaction between MUC1-expressing malignant cells, and Siglec-9-expressing immune cells in a tumor microenvironment was designed. Brief co-incubation of Siglec-9-expressing HEK293 cells, but not mock HEK293 cells, with MUC1-expressing cells similarly enhanced the recruitment of β-catenin to the MUC1 C-terminal domain. In addition, treatment of MUC1-expressing cells with neuraminidase almost completely abolished the effect of Siglec-9 on MUC1-mediated signaling. The recruited β-catenin was thereafter transported to the nucleus, leading to cell growth. These findings suggest that Siglec-9 expressed on immune cells may play a role as a potential counterreceptor for MUC1 and that this signaling may be another MUC1-mediated pathway and function in parallel with a growth factor-dependent pathway.
authors.affiliation: From the Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tanida
authors.forename: Kaoru
authors.initials: K
authors.lastname: Akita
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishida
authors.forename: Yugo
authors.initials: Y
authors.lastname: Mori
authors.forename: Munetoyo
authors.initials: M
authors.lastname: Toda
authors.forename: Mizue
authors.initials: M
authors.lastname: Inoue
authors.forename: Mariko
authors.initials: M
authors.lastname: Ohta
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yashiro
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Kosei
authors.initials: K
authors.lastname: Hirakawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakada
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D041681:NIH 3T3 Cells; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D055153:Stem Cell Niche / Q000235:genetics / Q000276:immunology; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology; D051176:beta Catenin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C060192:MUC1 protein, human; D018396:Mucin-1; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C422908:Siglece protein, mouse; D051176:beta Catenin; C577056:muc1 protein, mouse
keywords: Lectin; Mucins; Signaling; Tumor Microenvironment; β-Catenin
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