Loss of VHL expression contributes to epithelial-mesenchymal transition in oral squamous cell carcinoma.

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.

MATERIALS AND 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.

CONCLUSION: 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.