title: Smad7 maintains epithelial phenotype of ovarian cancer stem-like cells and supports tumor colonization by mesenchymal-epithelial transition.
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.
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Gong
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Ma
authors.affiliation: Shanghai Ji Ai Genetics and IVF Institute, Shanghai 200011, P.R. China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D034741:RNA, Small Interfering; D058985:Side-Population Cells; D051906:Smad7 Protein / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D034741:RNA, Small Interfering; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1