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Pluripotency factor Nanog is tumorigenic by deregulating DNA damage response in somatic cells

Oncogene volume 35, pages 1334–1340 (2016)Cite this article

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Abstract

The pluripotency gene Nanog is not expressed in normal adult tissues but is overexpressed in some human cancers. However, the tumorigenic roles of Nanog remain unclear. The ectopic expression of Nanog is not sufficient to induce spontaneous tumors in mice but can promote metastasis of established tumors by activating the expression of metastatic genes. The expression of Nanog in mouse skin activates tumor suppressor p53, leading to the differentiation of epidermal stem cells. In the absence of p53, Nanog induces spontaneous squamous cell carcinoma, identifying a novel role of Nanog in tumorigenesis. Therefore, the induction of p53 and differentiation in Nanog-expressing skin suppresses the tumorigenic activities of Nanog, which include the induction of DNA double-stranded break damage. Notably, Nanog interacts with the KRAB-associated protein 1 (KAP1) and inhibits its sumoylation activity, impairing KAP1-mediated chromatin remodeling, which is important for efficiently activating DNA damage response. In summary, Nanog is an oncogene with multiple roles in promoting tumorigenesis and metastasis.

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Acknowledgements

We thank Dr Manando Nakasaki for help with skin analysis, Dr Colin Jamora for providing K14-cre transgenic mice, and the UCSD Cancer Center Histology Core for help with the histological analysis. This work was supported by grants from Chinese Ministry of Science and Technology (2012CB966900 and 2013ZX10002008002) and CIRM (RC1-00148).

Author Contributions

JK and YX designed the experiments and analyzed the data. JK, YL and MQ executed the experiments. JK and YX were responsible for the initial draft of the manuscript and other authors contributed to the final edited versions.

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Authors and Affiliations

  1. Cancer Research Institute, Southern Medical University, Guangzhou, Guangdong, China

    J Kim, Y Liu & Y Xu

  2. Division of Biological Sciences, University of California, San Diego, La Jolla, CA, USA

    J Kim, M Qiu & Y Xu

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  1. J Kim
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  2. Y Liu
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  4. Y Xu
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Correspondence to Y Xu.

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Kim, J., Liu, Y., Qiu, M. et al. Pluripotency factor Nanog is tumorigenic by deregulating DNA damage response in somatic cells. Oncogene 35, 1334–1340 (2016). https://doi.org/10.1038/onc.2015.205

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