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NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer

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Tumor Biology

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.

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Acknowledgments

This study was funded by the Natural Science Foundation of Shanghai (12ZR1424300) and the National Natural Science Foundation (30600674).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 201600

    Suqing Liu, Jing Sun, Bin Cai, Xiaowei Xi, Liu Yang, Zhenbo Zhang, Youji Feng & Yunyan Sun

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  1. Suqing Liu
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Correspondence to Yunyan Sun.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of institutional and national research committees, with the 1964 Declaration of Helsinki and its later amendments or with comparable ethical standards.

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Liu, S., Sun, J., Cai, B. et al. NANOG regulates epithelial-mesenchymal transition and chemoresistance through activation of the STAT3 pathway in epithelial ovarian cancer. Tumor Biol. 37, 9671–9680 (2016). https://doi.org/10.1007/s13277-016-4848-x

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