Mesenchymal to Epithelial Transition Induced by Reprogramming Factors Attenuates the Malignancy of Cancer Cells.
Mesenchymal to Epithelial Transition Induced by Reprogramming Factors Attenuates the Malignancy of Cancer Cells.
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DOI：
10.1371/journal.pone.0156904
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Sano S
中科院分区：
文献类型：
--
作者：
Takaishi M;Tarutani M;Takeda J;Sano S
上皮细胞向间充质细胞转化（Epithelial to mesenchymal transition， EMT）是肿瘤转移的生物学过程。然而，一种直接针对EMT项目的有效抗癌疗法尚未被发现。最近的研究表明，在诱导多能干细胞的生成过程中，成纤维细胞观察到间充质向上皮转化（MET），即EMT的相反现象。在本研究中，我们研究了重编程因子（RFs）对鳞状细胞癌（SCC）细胞的影响。rfs引入的癌细胞（RICs）在形态学上表现出增强的上皮特征，mRNA和microRNAs的表达发生改变。RICs在体外的运动性和侵入性活动显著降低。此外，异种移植的RICs未出现淋巴结转移，而在亲代接种scc的小鼠中检测到转移。因此，我们得出结论，RICs通过MET恢复了上皮性质，并在体外和体内显示出肿瘤恶性程度的降低。因此，通过引入RFs来了解癌细胞中的MET过程可能会导致设计一种新的抗癌策略。
Epithelial to mesenchymal transition (EMT) is a biological process of metastatic cancer. However, an effective anticancer therapy that directly targets the EMT program has not yet been discovered. Recent studies have indicated that mesenchymal to epithelial transition (MET), the reverse phenomenon of EMT, is observed in fibroblasts during the generation of induced pluripotent stem cells. In the present study, we investigated the effects of reprogramming factors (RFs) on squamous cell carcinoma (SCC) cells. RFs-introduced cancer cells (RICs) demonstrated the enhanced epithelial characteristics in morphology with altered expression of mRNA and microRNAs. The motility and invasive activities of RICs in vitro were significantly reduced. Furthermore, xenografts of RICs exhibited no lymph node metastasis, whereas metastasis was detected in parental SCC-inoculated mice. Thus, we concluded that RICs regained epithelial properties through MET and showed reduced cancer malignancy in vitro and in vivo. Therefore, the understanding of the MET process in cancer cells by introduction of RFs may lead to the designing of a novel anticancer strategy.