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Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers

Oncogene volume 32, pages 3500–3509 (2013)Cite this article

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Abstract

Ovarian cancer is the most lethal of all gynecological malignancies, and the identification of novel prognostic and therapeutic targets for ovarian cancer is crucial. It is believed that only a small subset of cancer cells are endowed with stem cell properties, which are responsible for tumor growth, metastatic progression and recurrence. NANOG is one of the key transcription factors essential for maintaining self-renewal and pluripotency in stem cells. This study investigated the role of NANOG in ovarian carcinogenesis and showed overexpression of NANOG mRNA and protein in the nucleus of ovarian cancers compared with benign ovarian lesions. Increased nuclear NANOG expression was significantly associated with high-grade cancers, serous histological subtypes, reduced chemosensitivity, and poor overall and disease-free survival. Further analysis showed NANOG is an independent prognostic factor for overall and disease-free survival. Moreover, NANOG was highly expressed in ovarian cancer cell lines with metastasis-associated property and in clinical samples of metastatic foci. Stable knockdown of NANOG impeded ovarian cancer cell proliferation, migration and invasion, which was accompanied by an increase in mRNA expression of E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1. Conversely, ectopic NANOG overexpression enhanced ovarian cancer cell migration and invasion along with decreased E-cadherin, caveolin-1, FOXO1, FOXO3a, FOXJ1 and FOXB1 mRNA expression. Importantly, we found Nanog-mediated cell migration and invasion involved its regulation of E-cadherin and FOXJ1. This is the first report revealing the association between NANOG expression and clinical outcome of patients with ovarian cancers, suggesting NANOG to be a potential prognostic marker and therapeutic molecular target in ovarian cancer.

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Acknowledgements

We thank Dr Judy Yam for providing the anti-caveolin-1 antibody. The work was supported by funding from the Hong Kong Anti-Cancer Society Grant, Strategic Research Theme of Cancer Award and the Conference and Research grant from the University of Hong Kong.

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Authors and Affiliations

  1. Department of Pathology, University of Hong Kong, Queen Mary Hospital, Special Administrative Region of China, Hong Kong, China

    M K Y Siu, E S Y Wong, D S H Kong, H Y Chan, L Jiang, O G W Wong & A N Cheung

  2. Department of Surgery and Cancer, Imperial College London, London, UK

    E W-F Lam

  3. Department of Obstetrics and Gynaecology, University of Hong Kong, Queen Mary Hospital, Special Administrative Region of China, Hong Kong, China

    K K L Chan & H Y S Ngan

  4. Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    X-F Le

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  1. M K Y Siu
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Correspondence to M K Y Siu or A N Cheung.

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Siu, M., Wong, E., Kong, D. et al. Stem cell transcription factor NANOG controls cell migration and invasion via dysregulation of E-cadherin and FoxJ1 and contributes to adverse clinical outcome in ovarian cancers. Oncogene 32, 3500–3509 (2013). https://doi.org/10.1038/onc.2012.363

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