An essential role for N-cadherin and beta-catenin for progression in tongue squamous cell carcinoma and their effect on invasion and metastasis of Tca8113 tongue cancer cells.

摘要

It is well documented that adhesive molecules and catenins are closely associated with adhesion, invasion and metastasis in different types of tumors. Certain evidence indicates that another member of the cadherin family, N-cadherin, is expressed in highly invasive tumor cell lines that lacked E-cadherin expression. However, the role of N-cadherin in SCC of the tongue and relationship between N-cadherin and beta-catenin in SCC of the tongue remain unknown. Herein, the expressions of N/E-cadherin and beta-catenin were examined during the progression from normal tongue epithelium to invasive SCC of the tongue, the relationship between expressions of above proteins and clinicopathological characteristics in SCC of the tongue was analyzed. Further, we studied the effect of N-cadherin and beta-catenin on molecular mechanism of invasion and metastasis in SCC of the tongue. The results revealed that overexpression of N-cadherin and beta-catenin attributed to the progression of SCC of the tongue, whereas, E-cadherin showed a reverse result. In addition, the expressions of N-cadherin and beta-catenin were tightly associated with lymph node metastasis of SCC of the tongue (P<0.01). Furthermore, we transfected N-cadherin and beta-catenin siRNAs into Tca8113, a tongue SCC cell line, and analyzed the effects on cell migration, invasion, and metastasis in vitro. The results showed an obviously decreased invasion after transfection with N-cadherin or beta-catenin siRNAs compared to that of control and control siRNA, but after co-transfection with N-cadherin and beta-catenin siRNAs, a more profoundly decreased invasion was observed (P<0.05). In addition, after transfection with N-cadherin and beta-catenin siRNAs, down-regulation of N-cadherin and beta-catenin in Tca8113 cells gave rise to inhibition of invasion and metastasis of Tca8113 cells in vitro, probably associated with down-regulation of MMP-2 and MMP-9 proteins and up-regulation of the cell cycle inhibitor p21. Introduction of N-cadherin and beta-catenin siRNAs gave rise to proliferation suppression of the cells, accompanied with a cell cycle inhibition at the G0/G1 phase and cell apoptosis. These findings suggest that N-cadherin and beta-catenin are of vital importance in the invasion and metastasis of SCC of the tongue.