title: The c-Rel subunit of NF-κB is a crucial regulator of phenotype and motility of HaCaT keratinocytes.
abstract: The transcription factor NF-κB exerts key functions in epidermal homeostasis and carcinogenesis. Its c-Rel subunit is expressed in squamous cell carcinoma, and c-Rel down-regulation results in increased apoptosis, G2/M cell cycle delay with reduced proliferation and aberrant mitotic spindle formation. To further study the impact of c-Rel on essential keratinocyte features such as migration and epithelial morphology, c-Rel was down-regulated in HaCaT keratinocytes by a siRNA approach. This inhibition of c-Rel impaired the keratinocyte-typical clustered growth leading to a more scattered appearance of the cultures. The cells were more spindle-shaped and elongated, albeit without expression changes of markers characteristic for epithelial mesenchymal transition. In addition, wound healing-related migration and adhesion to type I collagen, fibronectin, laminin and vitronectin were significantly impaired. On the sub-cellular level, these functional features were not associated with quantitatively altered adhesion receptor or Rho-GTPase expression, but rather with a significantly reduced length of cell-matrix adhesion complexes and altered appearance of filamentous actin. Thus, our studies support a role for c-Rel in processes crucial for keratinocyte integrity and malignant transformation such as adhesion and migration.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany, verena.lorenz@med.uni-goettingen.de.
authors.forename: Verena Natalie
authors.initials: VN
authors.lastname: Lorenz
authors.forename: Michael P
authors.initials: MP
authors.lastname: Schön
authors.forename: Cornelia S
authors.initials: CS
authors.lastname: Seitz
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020573:Genes, rel / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D019096:Vitronectin / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D007797:Laminin; D016328:NF-kappa B; D034741:RNA, Small Interfering; D019096:Vitronectin; D020741:rho GTP-Binding Proteins