title: p53 modulates NF-κB mediated epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To investigate the role of p53 in NF-κB mediated epithelial-to-mesenchymal (EMT) in head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  We utilized HNSCC and normal oral epithelial cell lines as our model system. We used a lentiviral shRNA system to silence the expression of p65 and p53 in these cell lines. Mutant and wild-type (WT) p53 background genotypes were analyzed. The expression of epithelial and mesenchymal markers was determined using western blotting and quantitative PCR assays. Cell morphology, growth, and invasion were determined using a 3-dimensional spheroid culture and anchorage independent growth (AIG) assays.
  
  
  RESULTS
  In HNSCC cells with mutant p53 we found that silencing p65 expression promoted EMT. In contrast, in the context of WT p53, ectopic p65 over-expression promoted EMT. Ablation of WT p53 in normal oral epithelial cells blocked EMT induced by p65 over-expression. We demonstrate that AIG and apoptosis induced by NF-κB activation is regulated by p53.
  
  
  CONCLUSIONS
  Our data demonstrates that p53 mutational status is critical in determining the outcome of NF-κB activation in HNSCC. In the presence of WT p53, excess p65 signal can promote EMT. Conversely, ablation of p65 in the context of mutant p53 drives EMT. These results demonstrate that p53 mutational status alters the outcome of NF-κB signaling. These results, though preliminary, demonstrate the critical role of p53 mutational status in determining the outcome of NF-κB signaling and suggest that monitoring p53 status may inform the utility of NF-κB inhibitor treatment in HNSCC.
authors: Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States.
authors: Yuan
authors: Y
authors: Lin
authors: Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States.
authors: Jon
authors: J
authors: Mallen-St Clair
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States.
authors: Jie
authors: J
authors: Luo
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Veterans' Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States.
authors: Sherven
authors: S
authors: Sharma
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Veterans' Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States.
authors: Steven
authors: S
authors: Dubinett
authors: Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States. Electronic address: mstjohn@mednet.ucla.edu.
authors: Maie
authors: M
authors: St John
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Epithelial-to-mesenchymal transition; Head and neck cancer; NF-κB; p53; p65