title: Snail controls the mesenchymal phenotype and drives erlotinib resistance in oral epithelial and head and neck squamous cell carcinoma cells.
abstract: OBJECTIVE
  The presence of regional metastases in patients with head and neck squamous cell carcinoma (HNSCC) is a common and adverse event associated with poor prognosis. The authors' recent work on human HNSCC tissues underlies Snail's role as a molecular prognostic marker for HNSCC. Snail positivity is significantly predictive of poorly differentiated, lymphovascular invasive, and regionally metastatic tumors. Here, the authors investigate the capacity of Snail to drive epithelial-mesenchymal transition (EMT) in human oral epithelial cell lines and its ability to confer drug resistance.
  
  
  METHODS
  Snail was overexpressed in HNSCC and oral epithelial cell lines. Anchorage independent growth assays, wound healing assays, invasion and migration assays, spheroid modeling, and cell survival assays were performed.
  
  
  METHODS
  Academic tertiary medical center.
  
  
  METHODS
  Snail overexpressing HNSCC (OSC, Tu212, Tu686) and oral epithelial cell lines (HOK 16-B, OKF-6) were evaluated using assays for wound healing, invasion and migration, 3-dimensional growth, Western blot, and immunofluorescence.
  
  
  RESULTS
  The overexpression of Snail in human HNSCC and oral epithelial cell lines drives EMT. The transfection of Snail confers the expression of a mesenchymal molecular signature, including downregulation of the epithelial adherens, such as E-cadherin and β-catenin, and induction of mesenchymal markers. Snail-overexpressing cell lines demonstrate rapid growth in Anchorage-independent growth assays, a decreased capacity to form tight spheroids, an increased resistance to erlotinib, and an increased capacity for invasion.
  
  
  CONCLUSIONS
  Snail controls the mesenchymal phenotype and drives erlotinib resistance in HNSCC cells. Snail may prove to be a useful marker in predicting epidermal growth factor receptor inhibitor responsiveness.
authors.affiliation: Division of Head and Neck Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
authors.forename: Miranda
authors.initials: M
authors.lastname: Dennis
authors.forename: Guanyu
authors.initials: G
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.forename: Mariam
authors.initials: M
authors.lastname: Dohadwala
authors.forename: Elliot
authors.initials: E
authors.lastname: Abemayor
authors.forename: David A
authors.initials: DA
authors.lastname: Elashoff
authors.forename: Sherven
authors.initials: S
authors.lastname: Sharma
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.forename: Maie A
authors.initials: MA
authors.lastname: St John
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D016009:Chi-Square Distribution; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D000069347:Erlotinib Hydrochloride; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D011799:Quinazolines / Q000494:pharmacology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014945:Wound Healing; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D011799:Quinazolines; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D000069347:Erlotinib Hydrochloride