title: Binding of CD157 protein to fibronectin regulates cell adhesion and spreading.
abstract: CD157/BST-1 behaves both as an ectoenzyme and signaling receptor and is an important regulator of leukocyte trafficking and ovarian cancer progression. However, the molecular interactions underpinning the role of CD157 in these processes remain obscure. The biological functions of CD157 and its partnership with members of the integrin family prompted us to assume the existence of a direct interaction between CD157 and an unknown component of the extracellular matrix. Using solid-phase binding assays and surface plasmon resonance analysis, we demonstrated that CD157 binds fibronectin with high affinity within its heparin-binding domains 1 and 2. Furthermore, we found that CD157 binds to other extracellular matrix proteins containing heparin-binding domains. Finally, we proved that the CD157-fibronectin interaction occurs with living cells, where it elicits CD157-mediated cell responses. Indeed, knockdown of CD157 in Met-5A mesothelial cells changed their morphology and cytoskeleton organization and attenuated the activation of intracellular signaling pathways triggered by fibronectin. This led to impaired cell spreading and adhesion to selected extracellular matrix proteins. Collectively, these findings indicate a central role of CD157 in cell-extracellular matrix interactions and make CD157 an attractive therapeutic target in inflammation and cancer.
authors.affiliation: From the Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, 10126 Torino and.
authors.forename: Simona
authors.initials: S
authors.lastname: Morone
authors.affiliation: From the Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, 10126 Torino and.
authors.forename: Stefania
authors.initials: S
authors.lastname: Augeri
authors.affiliation: the School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cuccioloni
authors.affiliation: the School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Mozzicafreddo
authors.affiliation: the School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Angeletti
authors.affiliation: From the Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, 10126 Torino and.
authors.forename: Nicola
authors.initials: N
authors.lastname: Lo Buono
authors.affiliation: From the Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, 10126 Torino and.
authors.forename: Alice
authors.initials: A
authors.lastname: Giacomino
authors.affiliation: From the Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, 10126 Torino and.
authors.forename: Erika
authors.initials: E
authors.lastname: Ortolan
authors.affiliation: From the Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, 10126 Torino and ada.funaro@unito.it.
authors.forename: Ada
authors.initials: A
authors.lastname: Funaro
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000737:chemistry / Q000378:metabolism*; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology; D020349:Surface Plasmon Resonance
chemical_list: D015703:Antigens, CD; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D058851:GPI-Linked Proteins; D036541:ADP-ribosyl Cyclase; C087521:ADP-ribosyl cyclase 2
keywords: BST-1; CD157; Cell Adhesion; Cell Surface Receptor; Extracellular Matrix; Fibronectin; Heparin-binding Domain; Membrane Protein
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