title: Binding of a sialic acid-recognizing lectin Siglec-9 modulates adhesion dynamics of cancer cells via calpain-mediated protein degradation.
abstract: Although regulatory mechanisms for immune cells with inhibitory signals via immunoreceptor tyrosine-based inhibitory motifs are well known, signals transduced via interaction between Siglecs and sialyl compounds on their counterreceptors into target cells have not been reported to date. In this study, we found that an astrocytoma cell line, AS, showed detachment from culture plates when co-cultured with Siglec-9-expressing cells and/or soluble Siglec-9. Moreover, detached AS cells regrew as co-cultured cells with Siglec-9-deficient cells. They also showed increased motility and invasiveness upon Siglec-9 binding. In immunoblotting, rapid degradation of focal adhesion kinase (FAK) and related signaling molecules such as Akt, paxillin, and p130Cas was observed immediately after the co-culture. Despite degradation of these molecules, increased p-Akt was found at the front region of the cytoplasm, probably reflecting increased cell motility. Calpain was considered to be a responsible protease for the protein degradation by the inhibition experiments. These results suggest that protein degradation of FAK and related molecules was induced by Siglec-9 binding to its counterreceptors via sialylglycoconjugates, leading to the modulation of adhesion kinetics of cancer cells. Thus, this might be a mechanism by which cancer cells utilize Siglec-9-derived signals to escape from immunosurveillance.
authors.affiliation: From the Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-0065, Japan.
authors.forename: Ilhamjan
authors.initials: I
authors.lastname: Sabit
authors.forename: Noboru
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamaji
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D002154:Calpain / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D011975:Receptors, Mitogen / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D020298:U937 Cells
chemical_list: D015703:Antigens, CD; D009363:Neoplasm Proteins; D011975:Receptors, Mitogen; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D002154:Calpain
keywords: Adhesion; Calpain; Focal Adhesion Kinase; Lectin; Protein Degradation; Sialic Acid