title: Yes-associated protein expression in head and neck squamous cell carcinoma nodal metastasis.
abstract: BACKGROUND
  Yes-associated protein (YAP) is considered an oncogene found amplified in multiple tumors, including head and neck squamous cell carcinoma (HNSCC). However, the role for YAP expression in HNSCC is not understood. Based on the central role of YAP in the hippo pathway, we tested if YAP was associated with the stage of HNSCC progression and metastatic potential.
  
  
  METHODS
  To determine the expression of YAP in human benign and HNSCC tissue specimens, immunohistochemical analyses were performed in whole tissue samples and tissue microarrays. The expression of YAP in tissues of microarray was first associated with clinic-pathologic factors and results verified in samples from whole tissue sections. To investigate the role of YAP and p63 in regulating HNSCC epithelial to mesenchymal transition, epithelial and mesenchymal markers were assayed in Fadu and SCC-25 cells, HNSCC cells with endogenously elevated YAP expression and siRNA-mediated expression knockdown.
  
  
  RESULTS
  Analysis of human HNSCC tissues suggested YAP expression was elevated in tumors compared to benign tissues and specifically localized at the tumor invasive front (p value < 0.05). But, indexed YAP expression was lower with greater tumor grade (p value  =  0.02). In contrast, p63 expression was primarily elevated in high-grade tumors. Interestingly, both YAP and p63 was strongly expressed at the tumor invasive front and in metastatic HNSCC. Strikingly, we demonstrated YAP expression in the primary HNSCC tumor was associated with nodal metastasis in univariate analysis (p value  =  0.02). However, the knockdown of YAP in Fadu and SCC-25 cell lines was not associated with changes in epithelial to mesenchymal transdifferentiation or p63 expression.
  
  
  CONCLUSIONS
  Together, YAP expression, in combination with p63 can facilitate identification of HNSCC tumors from hyperplastic and benign tissues and the metastatic function of YAP in HNSCC may not be a result of epithelia to mesenchymal transdifferentiation.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ge
authors.forename: Matthew
authors.initials: M
authors.lastname: Smail
authors.forename: Wenxia
authors.initials: W
authors.lastname: Meng
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Kang-Hsien
authors.initials: KH
authors.lastname: Fan
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhou
authors.forename: Neil A
authors.initials: NA
authors.lastname: Bhowmick
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009687:Nuclear Proteins / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C456659:YY1AP1 protein, human
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