Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition

Li,Yiying; Gong,Wenjia; Ma,Xiaoling; Sun,Xiaoxi; Jiang,Hua; Chen,Tong

doi:10.3892/mmr.2014.2714

Smad7 maintains epithelial phenotype of ovarian cancer stem‑like cells and supports tumor colonization by mesenchymal‑epithelial transition

Authors:
- Yiying Li
- Wenjia Gong
- Xiaoling Ma
- Xiaoxi Sun
- Hua Jiang
- Tong Chen
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Affiliations: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China, Shanghai Ji Ai Genetics and IVF Institute, Shanghai 200011, P.R. China, Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
Published online on: October 21, 2014 https://doi.org/10.3892/mmr.2014.2714
Pages: 309-316

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Abstract

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‑β (TGF‑β)‑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‑β1 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‑β1 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‑β‑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.

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