title: Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors.
abstract: The non-receptor tyrosine kinase Syk is a well-characterized hematopoietic signal transducer, which is also expressed in non-hematopoietic cells. In epithelial cells, the function of Syk is not wholly known. It interacts with the receptor tyrosine kinase DDR1 and is frequently lost from metastatic mammary tumors. Here, using genetic tracing, we demonstrate Syk expression in murine mammary epithelium, myoepithelium and skin epithelium, but not in intestinal or lung epithelia. Investigating possible functions of Syk, we found a substantial suppression of cell mobility that depended on Syk kinase activity in trans-well migration and wounding assays. Co-expression of DDR1 resulted in constitutive interaction and strong activation of Syk kinase. Most importantly, Syk-mediated migration inhibition was blocked in the presence of DDR1, while conversely DDR1 knockdown restored migration inhibition. Our study identifies Syk as a potent inhibitor of epithelial migration and describes a first functional consequence of the interaction with the collagen receptor DDR1.
authors.affiliation: Department of Vascular Cell Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
authors.forename: Brit
authors.initials: B
authors.lastname: Neuhaus
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bühren
authors.forename: Barbara
authors.initials: B
authors.lastname: Böck
authors.forename: Frauke
authors.initials: F
authors.lastname: Alves
authors.forename: Wolfgang F
authors.initials: WF
authors.lastname: Vogel
authors.forename: Friedemann
authors.initials: F
authors.lastname: Kiefer
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D000070819:Discoidin Domain Receptor 1; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C083249:Ddr1 protein, mouse; D000070819:Discoidin Domain Receptor 1; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse