Repression of metastasis-associated protein 2 for inhibiting metastasis of human oral cancer cells by promoting the p-cofilin-1/ LC3-II expression.

Abstract

The overexpression of metastasis-associated protein 2 (MTA2) contributes to human tumor progression and metastasis in various tumor cells. However, the role of MTA2 in human oral cancer progression remains unknown. MTA2 expression in human oral tumor tissues and cell lines was measured by immunohistochemistry and Western blotting. Cell proliferation and cell cycle were analyzed using MTT assay and flow cytometry. The effects of MTA2 on oral cell migration and invasion were investigated using migration and invasion assays. The expression of MTA2, p-cofilin-1, and MTA2-induced LC3-II levels were measured using Western blotting and an immunofluorescence assay. Based on the human oral cancer tissue array and TCGA database, we found that MTA2 was increased in oral cancer tissues than in non-tumor oral tissues (P<.01). Moreover, MTA2 is significantly associated with tumor grade (P<.01) and the overall survival rate of patients with grade III tumor (P<.05). MTA2 expression in oral cancer cells was markedly higher than that in normal oral cells. Cell proliferation and cell cycle were not significantly changed in the cells inhibited by MTA2. MTA2 knockdown can inhibit cell migration and invasion of human oral cancer cells. Furthermore, we suggest that MTA2 inhibition enhances p-cofilin and LC3-II expression, and the knockdown of LC3-II expression in cells inhibited by MTA2 had the opposite effect. These results indicate that MTA2 may serve as a candidate prognostic biomarker and that targeting autophagy is a potential therapeutic strategy for treating human oral cancer.