title: p38 MAPK mediates epithelial-mesenchymal transition by regulating p38IP and Snail in head and neck squamous cell carcinoma.
abstract: In the present study, we investigated the role of p38-p38IP signaling in the inflammation-induced promotion of epithelial-to-mesenchymal transition (EMT) in Head and Neck Squamous Cell Carcinoma (HNSCC).
  
  
  
  Quantitative RT-PCR, western blot analysis, spheroid modeling and immunohistochemical staining of human HNSCC tissue sections were used.
  
  
  
  p38 inhibitor treated and p38 shRNA HNSCC cell lines demonstrate a significant upregulation in E-cadherin mRNA and a decrease in the mRNA expression of Snail. p38 binds to and stabilizes p38IP, a subunit of histone SPT3-TAF9-GCN5 acetyltransferase (STAGA), resulting in enhanced transcription of Snail. p38 shRNA HNSCC cell lines show a less invasive phenotype in a spheroid model. In clinical HNSCC samples, p38 interacting protein (p38IP) is significantly increased compared to adjacent normal tissue. An inverse relationship between p38, p38IP and E-cadherin is demonstrated.
  
  
  
  Herein we provide the first report that p38-p38IP is required for the Snail-induced E-cadherin down-regulation and cell invasion in HNSCC.
authors.affiliation: Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Head and Neck Surgery, United States.
authors.forename: Jon
authors.initials: J
authors.lastname: Mallen-St Clair
authors.affiliation: Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States.
authors.forename: Guanyu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Pathology and Laboratory Medicine, United States.
authors.forename: Fernando
authors.initials: F
authors.lastname: Palma-Diaz
authors.affiliation: Department of Pathology and Laboratory Medicine, United States.
authors.forename: Chi
authors.initials: C
authors.lastname: Lai
authors.affiliation: UCLA Head and Neck Cancer Program, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Elashoff
authors.affiliation: Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States; Department of Pathology and Laboratory Medicine, United States; Jonsson Comprehensive Cancer Center, United States; Department of Biostatistics, 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.forename: Sherven
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, United States; Division of Pulmonary and Critical Care Medicine, Department of Medicine, United States; Department of Pathology and Laboratory Medicine, United States; Jonsson Comprehensive Cancer Center, United States; Department of Biostatistics, 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.forename: Steven M
authors.initials: SM
authors.lastname: Dubinett
authors.affiliation: Department of Head and Neck Surgery, United States; Jonsson Comprehensive Cancer Center, United States; UCLA Head and Neck Cancer Program, United States. Electronic address: mstjohn@mednet.ucla.edu.
authors.forename: Maie
authors.initials: M
authors.lastname: St John
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015820:Cadherins; C502592:SUPT20H protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases
keywords: EMT; HNSCC; Snail; p38; p38IP