title: NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer.
abstract: NANOG is a key transcription factor that is overexpressed and plays an important role in various cancers. Its overexpression is associated with highly tumorigenic, drug-resistant, and poor prognosis. However, the underlying mechanism of action of NANOG in ovarian cancer remains unclear. Epithelial-mesenchymal transition (EMT), which is a critical process in cancer invasion and metastasis, is also associated with drug resistance. We determined whether NANOG is associated with EMT and chemoresistance in epithelial ovarian cancer cells. NANOG expression was increased in epithelial ovarian cancer cells (HEY and SKOV3) compared with normal epithelial ovarian cells (Moody). Low expression of NANOG increased the expression of E-cadherin and decreased the expression of vimentin, β-catenin, and Snail. Furthermore, the cell migration and invasion abilities were decreased. The multidrug resistance genes MDR-1 and GST-π were also downregulated when NANOG was lowly expressed. The cells that were transfected with the si-NANOG plasmid were more sensitive to cisplatin compared with the cells that were transfected with empty vector. The data demonstrated that Stat3 was correlated with NANOG-mediated EMT and drug resistance. The silencing of Stat3 expression abrogated NANOG-mediated EMT changes and increased the sensitivity of the cells to chemotherapy. These results suggest that NANOG mediates EMT and drug resistance through activation of the Stat3 pathway in epithelial ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600.
authors.forename: Suqing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600.
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xi
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600.
authors.forename: Youji
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600. sunyy2003@126.com.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D000071317:Nanog Homeobox Protein / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000235:genetics; D014162:Transfection / Q000379:methods; D014746:Vimentin / Q000235:genetics; D051176:beta Catenin / Q000235:genetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071250:Snail Family Transcription Factors; D014746:Vimentin; D051176:beta Catenin; D002945:Cisplatin
keywords: Chemoresistance; EMT; NANOG; Ovarian cancer; Stat3