Smad7 maintains epithelial phenotype of ovarian cancer stem-like cells and supports tumor colonization by mesenchymal-epithelial transition
Smad7 maintains epithelial phenotype of ovarian cancer stem-like cells and supports tumor colonization by mesenchymal-epithelial transition
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Smad7 维持卵巢癌干细胞样细胞的上皮表型并通过间充质-上皮转化支持肿瘤定植
DOI：
10.3892/mmr.2014.2714
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发表时间：
2015-01-01
影响因子：
3.4
通讯作者：
Chen, Tong
中科院分区：
文献类型：
--
作者：
Li, Yiying;Gong, Wenjia;Chen, Tong
上皮性卵巢癌是一种致命的妇科恶性肿瘤。上皮间质转化（EMT）在上皮性卵巢癌的发生、发展中起重要作用。在EMT过程中，转化生长因子-（TGF-）-Smad信号通路被认为调节细胞运动和肿瘤的发生发展。在众多EMT相关转录物中，Smad 7被认为是一种抑制剂，然而其与TGF-1一起参与卵巢癌的进展仍有待阐明。目前的研究表明，Smad 7在SK-OV-3和干细胞样侧群的EOC细胞中过表达，这两者都以上皮模式生长。TGF-1刺激细胞从上皮向间充质表型的转化，并相应增加SK-0 V-3细胞中Smad 7的表达。这些结果表明，Smad 7是在EOC细胞中维持上皮表型的调节器，并且可以作为靶向TGF-β刺激的EMT的抑制元件。此外，Smad 7的抑制导致细胞间充质转化，N-钙粘蛋白的表达增加和E-钙粘蛋白的表达减少。Smad 7小发夹RNA转导的EOC细胞的侵袭和迁移能力也降低。本研究的结果已经确定Smad 7作为维持上皮性卵巢癌细胞的上皮生长的基本因子。EMT的恢复导致间充质-上皮转变，这对于转移部位的EOC细胞定植是必要的。
Epithelial ovarian carcinoma (EOC) is a lethal gynecological malignancy. Epithelial-mesenchymal transition (EMT) has an important role in the tumorigenesis and progression of EOC. During the process of EMT, the transforming growth factor- (TGF-)-Smad signaling pathway has been indicated to regulate cell motility and tumor development. Among numerous EMT-associated transcripts, Smad7 is considered to be an inhibitor, however its involvement together with TGF-1 in the progression of ovarian cancer remains to be elucidated. The present study demonstrated that Smad7 was overexpressed in SK-OV-3 and stem-like side populations of EOC cells, both of which grow in an epithelial pattern. The transformation of cells from an epithelial to a mesenchymal phenotype was stimulated by TGF-1 with a corresponding increase in Smad7 expression in SK-OV-3 cells. These results indicate that Smad7 is a regulator in the maintenance of the epithelial phenotype in EOC cells, and may serve as an inhibitory element which targets TGF--stimulated EMT. Furthermore, inhibition of Smad7 resulted in cellular mesenchymal transformation, with an increased expression of N-cadherin and a decreased expression of E-cadherin. The invasiveness and migratory capabilities of Smad7 small hairpin RNA transduced EOC cells was also reduced. The findings of the present study have identified Smad7 as a fundamental factor in the maintenance of epithelial growth of EOC cells. Reversal of EMT results in a mesenchymal-epithelial transition, which is necessary for EOC cell colonization at metastatic sites.