Epithelial-mesenchymal transition associates with maintenance of stemness in spheroid-derived stem-like colon cancer cells.
Epithelial-mesenchymal transition associates with maintenance of stemness in spheroid-derived stem-like colon cancer cells.
复制标题
上皮-间质转化与球体来源的干样结肠癌细胞干性的维持相关。
DOI：
10.1371/journal.pone.0073341
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wei HB
中科院分区：
文献类型：
--
作者：
Han XY;Wei B;Fang JF;Zhang S;Zhang FC;Zhang HB;Lan TY;Lu HQ;Wei HB
尽管早期的研究证明了结肠癌干细胞（CCSCs）的特性和上皮间质转化（EMT）在肿瘤发生中的作用，但CCSCs和EMT之间的关系仍然存在争议。在这项研究中，为了深入了解结肠癌中的这种关系，我们开发了HCT 116和HT 29球体模型，它们被认为是富集癌症干细胞的细胞。与其亲本细胞相比，球状体细胞表现出较低的同型/异型粘附，但较高的体外迁移/侵袭能力，以及较高的体内致瘤性和转移潜力。E-cadherin表达下调，α-SMA和Vimentin表达上调，是EMT的典型表型。为了探讨这种现象是否与Wnt/β-catenin通路的激活有关，我们检测了几个关键的信号分子。与其亲本细胞相比，HCT 116和HT 29球形细胞中GSK 3 β的表达下调，Slug和Snail的表达上调。在球状体细胞中，胞核β-catenin表达上调，表明游离β-catenin由胞浆转移到胞核。我们的研究结果表明，球体细胞具有结肠癌干细胞的特征，EMT可能是其干细胞性和恶性的原因。Wnt/β-catenin通路的持续激活可能在CCSCs的EMT中起重要作用。
Despite earlier studies demonstrating characteristics of colon cancer stem cells (CCSCs) and the role of epithelial-mesenchymal transition (EMT) in tumor development, it remains controversial as to the relationship between CCSCs and EMT. In this study, in order to present an insight into this relationship in colon cancer, we developed HCT116 and HT29 sphere models, which are known to be the cells enriching cancer stem cells. Compared to their parental counterparts, spheroid cells displayed lower homotypic/heterotypic adhesion but higher in vitro migratory/invasive capacity, as well as higher tumorigenic and metastatic potential in vivo. The spheroid cells also demonstrated down-regulated E-cadherin and up-regulated α-SMA and Vimentin expression, which is the typical phenotype of EMT. In order to explore whether this phenomenon is associated to activation of Wnt/β-catenin pathway, we detected several key signaling molecules. Compared with their parental cells, HCT116 and HT29 spheroid cells demonstrated down-regulated expression of GSK3β, but up-regulated expression of Slug and Snail. And also, the up-regulation of nucleus β-catenin in spheroid cells indicated that the free β-catenin transferred from cytoplasm to cell nucleus. Our findings indicate that spheroid cells have the characteristics of colon cancer stem cells, and EMT may account for their stemness and malignancy. And persistent activation of Wnt/β-catenin pathway may play an important role in the EMT of CCSCs.
登录
查看更多内容
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
DOI：
10.1016/j.biocel.2003.09.004
发表时间：
2004-05-01
影响因子：
4
作者：
Buda, A;Pignatelli, M
通讯作者：
Pignatelli, M
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.
影响因子：
2.7
作者：
Brabletz, T;Hlubek, F;Kirchner, T
通讯作者：
Kirchner, T