Fucosyltransferase 2 (FUT2), the enzyme catalyzing α-1,2-fucosylation in mammals, has been implicated in cancer. The up-regulation of FUT2 has been observed in lung adenocarcinoma (LUAD), and FUT2 can enhance the cell migration and invasion of LUAD cell lines. However, the underlying mechanism of FUT2 in LUAD remains largely unknown. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during lung cancer metastasis and progression. In the present study, we showed that knocking down FUT2 in LUAD cell lines increased the expression of E-cadherin and reduced the expression of Vimentin, N-cadherin, TβRII, p-Smad2, p-Smad3 and Snail, which were the makers of EMT. Meanwhile, the expression of E-cadherin was decreased, and the expression of Vimentin was increased by restoring the expression of FUT2 in RNA interference FUT2 (RNAi-FUT2) cells, suggesting that FUT2 enhanced the EMT process in LUAD. Additionally, silencing FUT2 expression can up-regulate E-cadherin and down-regulate Vimentin, significantly attenuated EMT in vivo. Treated with the SIS3, a new-type inhibitor of p-Smad3 of TGF-β signaling, the expression of E-cadherin, Vimentin and Snail were not affected by RNAi-FUT2 cells, indicating that the effect of FUT2 on EMT depended on TGF-β/Smad signaling. Overall, the current results indicated that FUT2 might promote LUAD metastasis through the EMT initiated by TGF-β/Smad signaling. Therefore, FUT2 might be a prognostic factor and therapeutic target for LUAD.
Keywords: EMT; Fucosyltransferase 2; Lung adenocarcinaoma; TGF-β signaling pathway.
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