title: Epithelial-mesenchymal-transition induced by EGFR activation interferes with cell migration and response to irradiation and cetuximab in head and neck cancer cells.
abstract: OBJECTIVE
  The role of epithelial-mesenchymal transition (EMT) in the poor outcome of EGFR-overexpressing SCCHN was evaluated.
  
  
  METHODS
  SCCHN cell lines were characterized for their cell morphology and expression of EGFR and the EMT-associated factors E-cadherin, vimentin and Snail1. The migratory potential of cells was assessed in motility assays. Response to irradiation and cetuximab was determined using clonogenic survival assays.
  
  
  RESULTS
  High basal expression of E-cadherin but low to absent vimentin expression could be observed in all SCCHN cell lines. Although E-cadherin expression levels did not change after treatment with EGF we observed a significant change in cell morphology resembling EMT. SCCHN cells with high basal levels of Snail1 resulting from constitutive EGFR activation were characterized by mesenchymal-like morphology, elevated migratory potential, reduced sensitivity to irradiation and cetuximab but increased sensitivity to the combined treatment.
  
  
  CONCLUSIONS
  Autocrine activation of EGFR leading to EMT is associated with a metastatic phenotype and reduced sensitivity of SCCHN cells to single-modality treatment with cetuximab or irradiation. The potential of Snail1 as biomarker for selection of patients who will mostly benefit from a combination of cetuximab and radiotherapy has to be evaluated in future clinical studies.
authors.affiliation: Laboratory for Translational Radiobiology & Radiooncology, Department of Radiooncology, Charité Campus Mitte, Berlin, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Holz
authors.forename: Franziska
authors.initials: F
authors.lastname: Niehr
authors.forename: Mariya
authors.initials: M
authors.lastname: Boyko
authors.forename: Tsvetana
authors.initials: T
authors.lastname: Hristozova
authors.forename: Luitpold
authors.initials: L
authors.lastname: Distel
authors.forename: Volker
authors.initials: V
authors.lastname: Budach
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Tinhofer
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000528:radiation effects*; D000068818:Cetuximab; D059248:Chemoradiotherapy; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D015151:Immunoblotting; D011839:Radiation, Ionizing; D060888:Real-Time Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D066246:ErbB Receptors; D000068818:Cetuximab