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Reprogramming activity of NANOGP8, a NANOG family member widely expressed in cancer

Oncogene volume 33, pages 2513–2519 (2014)Cite this article

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Abstract

NANOG is a key transcription factor for pluripotency in embryonic stem cells. The analysis of NANOG in human cells is confounded by the presence of multiple and highly similar paralogs. In particular, there are three paralogs encoding full-length proteins, namely, NANOG1, NANOG2 and NANOGP8, and at least eight additional paralogs that do not encode full-length NANOG proteins. Here, we have examined NANOG family expression in human embryonic stem cells (hESCs) and in human cancer cell lines using a multi-NANOG PCR that amplifies the three functional paralogs and most of the non-functional ones. As anticipated, we found that hESCs express large amounts of NANOG1 and, interestingly, they also express NANOG2. In contrast, most human cancer cells tested express NANOGP8 and the non-coding paralogs NANOGP4 and NANOGP5. Notably, in some cancer cell lines, the NANOG protein levels produced by NANOGP8 are comparable to those produced by NANOG1 in pluripotent cells. Finally, we show that NANOGP8 is as active as NANOG1 in the reprogramming of human and murine fibroblasts into induced pluripotent stem cells. These results show that cancer-associated NANOGP8 can contribute to promote de-differentiation and/or cellular plasticity.

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Acknowledgements

We are grateful to Dr Maria S Soengas (CNIO) for providing us with human primary fibroblasts and to Dr Miguel A Piris (CNIO) for providing us with all the human cancer cell lines. ARP is supported by the FPI Program of the Spanish Department of Science (MINECO). DP was funded by an EMBO Long-Term Fellowship. HL is supported by the ‘Ramon y Cajal’ Program (MINECO). Work in the laboratory of MS is funded by the CNIO and by grants from the MINECO (SAF), the European Union (ERC Advanced Grant), the Regional Government of Madrid, the Botin Foundation, the Ramon Areces Foundation and the AXA Foundation. Work in the laboratory of EFW is supported by grants from F-BBVA and the European Union (ERC Advanced Grant).

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Authors and Affiliations

  1. Tumour Suppression Group, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    A R Palla, D Piazzolla, M Abad, H Li & M Serrano

  2. Genomics Core Unit, Biotechnology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    O Dominguez

  3. Genes, Development and Disease Group, F-BBVA–CNIO Cancer Cell Biology Programme, Spanish National Cancer Research Center (CNIO), Madrid, Spain

    H B Schonthaler & E F Wagner

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  1. A R Palla
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Correspondence to M Serrano.

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Palla, A., Piazzolla, D., Abad, M. et al. Reprogramming activity of NANOGP8, a NANOG family member widely expressed in cancer. Oncogene 33, 2513–2519 (2014). https://doi.org/10.1038/onc.2013.196

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