Autophagy modulates transforming growth factor beta 1 induced epithelial to mesenchymal transition in non-small cell lung cancer cells Check
Autophagy modulates transforming growth factor beta 1 induced epithelial to mesenchymal transition in non-small cell lung cancer cells Check
复制标题
自噬调节转化生长因子β 1诱导的非小细胞肺癌细胞上皮向间质转化
DOI：
10.1016/j.bbamcr.2018.02.007
复制
发表时间：
2018-05-01
影响因子：
5.1
通讯作者：
Ghavami, Saeid
中科院分区：
文献类型：
--
作者：
Alizadeh, Javad;Glogowska, Aleksandra;Ghavami, Saeid
肺癌被认为是全球癌症相关死亡的最常见原因之一，非小细胞肺癌（NSCLC）占所有肺癌病例的80%。自噬是一种细胞过程，负责回收受损的细胞器和蛋白质聚集体。转化生长因子β-1（TGF β 1）参与不同癌症模型中的上皮细胞向间质细胞转化（EMT）和自噬诱导，并在NSCLC的发病机制中发挥重要作用。目前尚不清楚自噬如何调节NSCLC细胞中的EMT。在本研究中，我们研究了自噬在NSCLC EMT诱导中的调节作用，并表明TGF β 1可以同时诱导NSCLC细胞系A549和H1975中的自噬和EMT。在使用巴非霉素-A1化学抑制自噬后，间充质标志物波形蛋白和N-钙粘蛋白的表达减少。免疫印迹和免疫细胞化学（ICC）显示，与用scramble shRNA处理的相应细胞（阴性对照）相比，TGF β 1处理后，ATG 7敲减细胞中的间充质标记物波形蛋白显著下调，而E-cadherin没有变化。此外，自噬抑制（巴弗洛霉素Al和ATG 7敲低）降低了TGF β（1）处理后NSCLC细胞的两种重要间充质功能，即迁移和收缩。这项研究确定了自噬作为NSCLC细胞中TGF β（1）诱导EMT的潜在正调节剂的关键作用，并确定了自噬抑制剂作为拮抗EMT诱导剂（如TGF β（1））在NSCLC临床进展中作用的有前途的新药。
Lung cancer is considered one of the most frequent causes of cancer-related death worldwide and Non-Small Cell Lung Cancer (NSCLC) accounts for 80% of all lung cancer cases. Autophagy is a cellular process responsible for the recycling of damaged organelles and protein aggregates. Transforming growth factor beta-1 (TGF beta(1)) is involved in Epithelial to Mesenchymal Transition (EMT) and autophagy induction in different cancer models and plays an important role in the pathogenesis of NSCLC. It is not clear how autophagy can regulate EMT in NSCLC cells. In the present study, we have investigated the regulatory role of autophagy in EMT induction in NSCLC and show that TGF beta(1) can simultaneously induce both autophagy and EMT in the NSCL lines A549 and H1975. Upon chemical inhibition of autophagy using Bafilomycin-A1, the expression of the mesenchymal marker vimentin and N-cadherin was reduced. Immunoblotting and immunocytochemistry (ICC) showed that the mesenchymal marker vimentin was significantly downregulated upon TGF beta(1) treatment in ATG7 knockdown cells when compared to corresponding cells treated with scramble shRNA (negative control), while E-cadherin was unchanged. Furthermore, autophagy inhibition (Bafilomycin Al and ATG7 knockdown) decreased two important mesenchymal functions, migration and contraction, of NSCLC cells upon TGF beta(1) treatment. This study identified a crucial role of autophagy as a potential positive regulator of TGF beta(1) -induced EMT in NSCLC cells and identifies inhibitors of autophagy as promising new drugs in antagonizing the role of EMT inducers, like TGF beta(1), in the clinical progression of NSCLC.