Fucosyltransferase 2 induced epithelial-mesenchymal transition via TGF-β Smad signaling pathway in lung adenocarcinaoma
Fucosyltransferase 2 induced epithelial-mesenchymal transition via TGF-β Smad signaling pathway in lung adenocarcinaoma
复制标题
岩藻糖基转移酶 2 通过 TGF-β Smad 信号通路诱导肺腺癌上皮间质转化
DOI：
10.1016/j.yexcr.2018.07.026
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发表时间：
2018-09-15
影响因子：
3.7
通讯作者：
Chen, Xiaoming
中科院分区：
文献类型：
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作者：
Deng, Guoqing;Chen, Lvao;Chen, Xiaoming
岩藻糖基转移酶2（FUT 2）是哺乳动物中催化α-1，2-岩藻糖基化的酶，与癌症有关。FUT 2在肺腺癌中表达上调，并能增强LUAD细胞的迁移和侵袭能力。然而，LUAD中FUT 2的潜在机制在很大程度上仍然未知。大量研究表明，上皮-间质转化（EMT）在肺癌转移和进展过程中发挥着关键作用。在本研究中，我们发现在LUAD细胞系中敲低FUT 2增加了E-cadherin的表达，并减少了Vimentin、N-cadherin、T β RII、p-Smad 2、p-Smad 3和Snail的表达，这些都是EMT的标志物。同时，通过恢复FUT 2在RNA干扰FUT 2（RNAi-FUT 2）细胞中的表达，E-cadherin的表达降低，Vimentin的表达增加，提示FUT 2增强了LUAD的EMT过程。此外，沉默FUT 2表达可上调E-钙粘蛋白并下调波形蛋白，从而显著减弱体内EMT。经新型TGF-β信号通路p-Smad 3抑制剂SIS 3处理后，E-cadherin、Vimentin和Snail的表达不受RNAi-FUT 2细胞的影响，表明FUT 2对EMT的影响依赖于TGF-β/Smad信号通路。总之，目前的结果表明，FUT 2可能通过TGF-β/Smad信号启动的EMT促进LUAD转移。因此，FUT 2可能是LUAD的预后因子和治疗靶点。
Fucosyltransferase 2 (FUT2), the enzyme catalyzing alpha-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, T beta RII, 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-beta 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-beta/Smad signaling. Overall, the current results indicated that FUT2 might promote LUAD metastasis through the EMT initiated by TGF-beta/Smad signaling. Therefore, FUT2 might be a prognostic factor and therapeutic target for LUAD.