title: Cleavage of syndecan-4 by ADAMTS1 provokes defects in adhesion.
abstract: Syndecan-4 is a membrane-bound heparan sulfate proteoglycan that participates in cell-cell and cell-matrix interactions and modulates adhesion and migration of many cell types. Through its extracellular domain, syndecan-4 cooperates with adhesion molecules and binds matrix components relevant for cell migration. Importantly, syndecan-4 is a substrate of extracellular proteases, however the biological significance of this cleavage has not been elucidated. Here, we show that the secreted metalloprotease ADAMTS1, involved in angiogenesis and inflammatory processes, cleaves the ectodomain of syndecan-4. We further showed that this cleavage results in altered distribution of cytoskeleton components, functional loss of adhesion, and gain of migratory capacities. Using syndecan-4 null cells, we observed that ADAMTS1 proteolytic action mimics the outcome of genetic deletion of this proteoglycan with regards to focal adhesion. Our findings suggest that the shedding of syndecan-4 by ADAMTS1 disrupts cell adhesion and promotes cell migration.
authors.affiliation: Medical Oncology Research Program, Vall d'Hebron University Hospital Research Institute/Universidad Autónoma de Barcelona, Barcelona 08035, Spain. juancarlos.rodriguez@genyo.es
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Rodríguez-Manzaneque
authors.forename: Darren
authors.initials: D
authors.lastname: Carpizo
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: Plaza-Calonge
authors.forename: Antoni Xavier
authors.initials: AX
authors.lastname: Torres-Collado
authors.forename: Shelley N-M
authors.initials: SN
authors.lastname: Thai
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
authors.forename: Arie
authors.initials: A
authors.lastname: Horowitz
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Iruela-Arispe
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D022001:Focal Adhesions / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011348:Procollagen N-Endopeptidase / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D053671:Syndecan-4 / Q000378:metabolism*; D014162:Transfection
chemical_list: D000199:Actins; D006025:Glycosaminoglycans; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508304:SDC4 protein, human; D053671:Syndecan-4; D045726:Metalloproteases; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein
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