title: Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma.
abstract: Cell migration is regulated by adhesion to the extracellular matrix (ECM) through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC). We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad) or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad), plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization.
authors.affiliation: Basic Research Center, Dentistry School, Federal University of Rio Grande of Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Grasieli de Oliveira
authors.initials: Gde O
authors.lastname: Ramos
authors.affiliation: Basic Research Center, Dentistry School, Federal University of Rio Grande of Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Lisiane
authors.initials: L
authors.lastname: Bernardi
authors.affiliation: Basic Research Center, Dentistry School, Federal University of Rio Grande of Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Isabel
authors.initials: I
authors.lastname: Lauxen
authors.affiliation: Basic Research Center, Dentistry School, Federal University of Rio Grande of Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Manoel
authors.initials: M
authors.lastname: Sant'Ana Filho
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Alan Rick
authors.initials: AR
authors.lastname: Horwitz
authors.affiliation: Basic Research Center, Dentistry School, Federal University of Rio Grande of Sul, Porto Alegre, Rio Grande do Sul, Brazil.|Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil.|Department of Morphological Sciences, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
authors.forename: Marcelo Lazzaron
authors.initials: ML
authors.lastname: Lamers
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D015820:Cadherins; D005353:Fibronectins