Lu Xiaoxiao, Guo Honglan, Chen Xi, Xiao Jian, Zou Yong, Wang Wei, Chen Qiong
Department of Geriatrics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Oncol Rep. 2016 Dec;36(6):3105-3112. doi: 10.3892/or.2016.5146. Epub 2016 Oct 4.
According to recent research, Ras homolog gene family member C (RhoC) is confirmed to have a powerful regulatory effect on cell motility mediated by the cytoskeleton, and this process is closely associated with tumor invasion and metastasis. In addition, the epithelial-mesenchymal transition (EMT) process which causes cytoskeleton rearrangement, also plays a pivotal role in tumor invasion and metastasis.Consequently, in the present study, we aimed to ascertain whether RhoC has an effect on the EMT process induced by TGF-β1 in lung adenocarcinoma cells and whether RhoC promotes tumor invasion by mediating the occurrence of EMT. Based on the findings, we demonstrated that RhoC was an essential mediator of the EMT process in lung adenocarcinoma cell line A549 which was evaluated by observing the morphological characteristics of the cells and by assessing the expression levels of two EMT marker proteins: E-cadherin and vimentin. During the process of EMT in the A549 cells induced by TGF-β1 (5 ng/ml), upregulated RhoC protein and RhoC activity were detected, which was associated with the enhanced invasive capability of the cells in vitro. Conversely, downregulation of the expression of RhoC by shRNA markedly impeded EMT progression as well as the invasion of A549 cells. Our results may provide a novel target towards the prevention of metastasis in advanced lung adenocarcinoma.
根据最近的研究，Ras同源基因家族成员C（RhoC）被证实对由细胞骨架介导的细胞运动具有强大的调节作用，并且这一过程与肿瘤侵袭和转移密切相关。此外，导致细胞骨架重排的上皮-间质转化（EMT）过程在肿瘤侵袭和转移中也起着关键作用。因此，在本研究中，我们旨在确定RhoC是否对肺腺癌细胞中由转化生长因子-β1（TGF-β1）诱导的EMT过程有影响，以及RhoC是否通过介导EMT的发生促进肿瘤侵袭。基于这些发现，我们证明RhoC是肺腺癌细胞系A549中EMT过程的重要介导因子，这是通过观察细胞的形态特征以及评估两种EMT标志物蛋白：E-钙黏蛋白和波形蛋白的表达水平来评估的。在由TGF-β1（5 ng/ml）诱导的A549细胞EMT过程中，检测到RhoC蛋白上调和RhoC活性增加，这与细胞在体外增强的侵袭能力相关。相反，通过短发夹RNA（shRNA）下调RhoC的表达明显阻碍了EMT进程以及A549细胞的侵袭。我们的结果可能为晚期肺腺癌转移的预防提供一个新的靶点。
