Takaishi Mikiro, Tarutani Masahito, Takeda Junji, Sano Shigetoshi
Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.
Department of Social and Environmental Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
PLoS One. 2016 Jun 3;11(6):e0156904. doi: 10.1371/journal.pone.0156904. eCollection 2016.
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.
上皮-间质转化（EMT）是转移性癌症的一个生物学过程。然而，尚未发现直接靶向EMT程序的有效抗癌疗法。最近的研究表明，在诱导多能干细胞产生过程中，在成纤维细胞中观察到了间质-上皮转化（MET），即EMT的逆向现象。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。引入RFs的癌细胞（RICs）在形态上表现出增强的上皮特征，同时mRNA和微小RNA的表达发生改变。RICs在体外的运动性和侵袭活性显著降低。此外，RICs的异种移植未表现出淋巴结转移，而在接种亲本SCC的小鼠中检测到了转移。因此，我们得出结论，RICs通过MET恢复了上皮特性，并在体外和体内显示出降低的癌症恶性程度。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出一种新的抗癌策略。
