title: Loss of VHL expression contributes to epithelial-mesenchymal transition in oral squamous cell carcinoma.
abstract: OBJECTIVE
  Loss of Von Hippel-Lindau (VHL) gene expression has been implicated in the development of human cancers. However, its function in oral squamous cell carcinoma (OSCC) remains undefined. The aim of this study was to clarify the VHL expression in OSCC and to explore the underlying mechanisms of VHL in modulating the epithelial-mesenchymal transition (EMT) in OSCC.
  
  
  METHODS
  The expression of VHL, HIF-1α and EMT related proteins in OSCC tissues were evaluated by immunohistochemistry. The correlation of VHL with clinico-pathological characteristics, prognosis and EMT related proteins were analyzed. The roles of VHL on the cell morphology, proliferation, migration, and invasion were determined by MTT, scratch and transwell invasion assay in Tscca and Tca8113P160 cells. The EMT related proteins were determined by Western blot and immunofluorescence (IF) methods.
  
  
  RESULTS
  Loss of VHL expression was closely associated with pathologic grading, lymph node metastasis, poor prognosis, and EMT in OSCC. After re-expression of VHL, there was a cell morphologic change and motivation, proliferation, invasion of the cells were inhibited. The expression of Snail, N-cadherin and MMP-2/9, HIF-1α and VEGF were down-regulated in both the cell lines after transfection with VHL plasmid, while E-cadherin was up-regulated. Moreover, the effect of VHL suppressing β-catenin accumulation in nucleus was proved by Western blot and IF.
  
  
  CONCLUSIONS
  VHL was significantly correlated with EMT process of OSCC. β-Catenin was an important downstream gene of VHL besides HIF-1α, which could induce the EMT process in OSCC.
authors.affiliation: Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Su
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Yue
authors.affiliation: Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Maxillofacial and E.N.T Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Electronic address: wxd.1133@163.com.
authors.forename: Xudong
authors.initials: X
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: Epithelial–mesenchymal transition; Oral squamous cell carcinoma; VHL; β-Catenin