Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

doi:10.1038/ncomms5226

. 2014 Jun 30:5:4226.

doi: 10.1038/ncomms5226.

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

Daniela Piazzolla¹, Adelaida R Palla², Cristina Pantoja², Marta Cañamero³, Ignacio Perez de Castro⁴, Sagrario Ortega⁵, Gonzalo Gómez-López⁶, Orlando Dominguez⁷, Diego Megías⁸, Giovanna Roncador⁹, Jose L Luque-Garcia¹⁰, Beatriz Fernandez-Tresguerres¹¹, Agustin F Fernandez¹², Mario F Fraga¹³, Manuel Rodriguez-Justo¹⁴, Miguel Manzanares¹¹, Marta Sánchez-Carbayo¹⁵, Juana María García-Pedrero¹⁶, Juan P Rodrigo¹⁶, Marcos Malumbres⁴, Manuel Serrano¹

Affiliations

¹ Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
² 1] Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain [2].
³ Histopathology Core Unit, CNIO, Madrid 28029, Spain.
⁴ Cell Division and Cancer Group, CNIO, Madrid 28029, Spain.
⁵ Transgenic Mice Core Unit, CNIO, Madrid 28029, Spain.
⁶ Bioinformatics Unit, CNIO, Madrid 28029, Spain.
⁷ Genomics Core Unit, CNIO, Madrid 28029, Spain.
⁸ Confocal Microscopy Core Unit, CNIO, Madrid 28029, Spain.
⁹ Monoclonal Antibodies Core Unit, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
¹⁰ Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Madrid 28040, Spain.
¹¹ Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
¹² Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain.
¹³ 1] Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain [2] Department of Immunology and Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Madrid 28049, Spain.
¹⁴ Department of Pathology, University College Hospital, London NW1 2BU, UK.
¹⁵ CIC bioGUNE, Bizkaia Technology Park, Derio 48160 and Ikerbasque, Basque Foundation for Science, Bilbao 48011, Spain.
¹⁶ Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo 33006, Spain.

PMID: 24979572
DOI: 10.1038/ncomms5226

Free article

Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

Daniela Piazzolla et al. Nat Commun. 2014.

Free article

. 2014 Jun 30:5:4226.

doi: 10.1038/ncomms5226.

Authors

Affiliations

¹ Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
² 1] Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain [2].
³ Histopathology Core Unit, CNIO, Madrid 28029, Spain.
⁴ Cell Division and Cancer Group, CNIO, Madrid 28029, Spain.
⁵ Transgenic Mice Core Unit, CNIO, Madrid 28029, Spain.
⁶ Bioinformatics Unit, CNIO, Madrid 28029, Spain.
⁷ Genomics Core Unit, CNIO, Madrid 28029, Spain.
⁸ Confocal Microscopy Core Unit, CNIO, Madrid 28029, Spain.
⁹ Monoclonal Antibodies Core Unit, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
¹⁰ Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Madrid 28040, Spain.
¹¹ Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
¹² Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain.
¹³ 1] Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain [2] Department of Immunology and Oncology, Centro Nacional de Biotecnología/CNB-CSIC, Madrid 28049, Spain.
¹⁴ Department of Pathology, University College Hospital, London NW1 2BU, UK.
¹⁵ CIC bioGUNE, Bizkaia Technology Park, Derio 48160 and Ikerbasque, Basque Foundation for Science, Bilbao 48011, Spain.
¹⁶ Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo 33006, Spain.

PMID: 24979572
DOI: 10.1038/ncomms5226

Abstract

NANOG is a pluripotency transcription factor in embryonic stem cells; however, its role in adult tissues remains largely unexplored. Here we show that mouse NANOG is selectively expressed in stratified epithelia, most notably in the oesophagus where the Nanog promoter is hypomethylated. Interestingly, inducible ubiquitous overexpression of NANOG in mice causes hyperplasia selectively in the oesophagus, in association with increased cell proliferation. NANOG transcriptionally activates the mitotic programme, including Aurora A kinase (Aurka), in stratified epithelia, and endogenous NANOG directly binds to the Aurka promoter in primary keratinocytes. Interestingly, overexpression of Nanog or Aurka in mice increased proliferation and aneuploidy in the oesophageal basal epithelium. Finally, inactivation of NANOG in cell lines from oesophageal or head and neck squamous cell carcinomas (ESCCs or HNSCCs, respectively) results in lower levels of AURKA and decreased proliferation, and NANOG and AURKA expression are positively correlated in HNSCCs. Together, these results indicate that NANOG has a lineage-restricted mitogenic function in stratified epithelia.

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Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

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Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia

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