轉移相關蛋白2經由促進p-cofilin-1/LC3-II的表達來抑制人類口腔癌細胞的轉移

背景：轉移相關蛋白2（MTA2）的過表達有助於人類各種腫瘤細胞的進展和轉移。然而，MTA2在人類口腔癌中的作用機轉仍然未知。材料和方法：通過免疫組織化學法和西方墨點法來觀察 MTA2在人口腔腫瘤組織中的表達情形。使用細胞存活率分析法(MTT assay)分析細胞增殖的狀況以及流式細胞儀觀察細胞週期。使用細胞遷移和侵襲測定法研究來看MTA2對口腔細胞遷移和侵襲的影響。MTA2與p-cofilin-1的表達，以及MTA2誘導LC3-II的表達分別使用西方墨點法和免疫螢光測定法測定。結果:由人類口腔癌組織陣列和TCGA數據庫中，我們發現口腔癌組織中的MTA2表達比在鄰近正常口腔組織中（p <0.01）明顯增加。而且，MTA2的表達明顯與口腔癌期數有相關（p <0.01），其中的口腔癌患者(Grade III)中，MTA2的表達與總生存率明顯相關（p <0.05）。但抑制MTA2則與細胞增殖和細胞週期無明顯相關。我們也發現，抑制MTA2可以抑制口腔癌細胞的細胞遷移和侵襲。此外，我們發現藉由抑制MTA2可增強p-cofilin和LC3-II表達，反之，抑制LC3-II的表達，則MTA2會得到相反的結果。結論：這些結果顯示MTA2也許可以作為預估預後的生物性指標，而靶向自噬作用具有治療人類口腔癌的潛力。

Background: 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. Materials and methods: 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. Results: 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. Moreover, MTA2 is significantly associated with tumor grade and the overall survival rate of patients with grade III tumor. 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. Conclusion: 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.