title: Discoidin domain receptor 2 is a critical regulator of epithelial-mesenchymal transition.
abstract: Discoidin domain receptor 2 (DDR2) is a collagen receptor that is expressed during epithelial-mesenchymal transition (EMT), a cellular transformation that mediates many stages of embryonic development and disease. However, the functional significance of this receptor in EMT is unknown. Here we show that Transforming Growth Factor-beta1 (TGF-β1), a common stimulator of EMT, promotes increased expression of type I collagen and DDR2. Inhibiting expression of COL1A1 or DDR2 with siRNA is sufficient to perturb activity of the NF-κB and LEF-1 transcription factors and to inhibit EMT and cell migration induced by TGF-β1. Furthermore, knockdown of DDR2 expression with siRNA inhibits EMT directly induced by type I collagen. These data establish a critical role for type I collagen-dependent DDR2 signaling in the regulation of EMT.
authors.affiliation: Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Logan A
authors.initials: LA
authors.lastname: Walsh
authors.forename: Ali
authors.initials: A
authors.lastname: Nawshad
authors.forename: Damian
authors.initials: D
authors.lastname: Medici
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000070818:Discoidin Domain Receptors; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: D015820:Cadherins; D024042:Collagen Type I; D011975:Receptors, Mitogen; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D008156:Luciferases; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases