Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia
Daniela Piazzolla,
Adelaida R. Palla,
Cristina Pantoja,
Marta Cañamero,
Ignacio Perez de Castro,
Sagrario Ortega,
Gonzalo Gómez-López,
Orlando Dominguez,
Diego Megías,
Giovanna Roncador,
Jose L. Luque-Garcia,
Beatriz Fernandez-Tresguerres,
Agustin F. Fernandez,
Mario F. Fraga,
Manuel Rodriguez-Justo,
Miguel Manzanares,
Marta Sánchez-Carbayo,
Juana María García-Pedrero,
Juan P. Rodrigo,
Marcos Malumbres and
Manuel Serrano ()
Additional contact information
Daniela Piazzolla: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO)
Adelaida R. Palla: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO)
Cristina Pantoja: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO)
Marta Cañamero: Histopathology Core Unit, CNIO
Ignacio Perez de Castro: CNIO
Sagrario Ortega: Transgenic Mice Core Unit, CNIO
Gonzalo Gómez-López: Bioinformatics Unit, CNIO
Orlando Dominguez: Genomics Core Unit, CNIO
Diego Megías: Confocal Microscopy Core Unit, CNIO
Giovanna Roncador: Monoclonal Antibodies Core Unit, Spanish National Cancer Research Centre (CNIO)
Jose L. Luque-Garcia: Faculty of Chemistry, Complutense University of Madrid
Beatriz Fernandez-Tresguerres: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Agustin F. Fernandez: Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo
Mario F. Fraga: Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo
Manuel Rodriguez-Justo: University College Hospital
Miguel Manzanares: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
Marta Sánchez-Carbayo: CIC bioGUNE, Bizkaia Technology Park, Derio 48160 and Ikerbasque, Basque Foundation for Science
Juana María García-Pedrero: Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo
Juan P. Rodrigo: Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo
Marcos Malumbres: CNIO
Manuel Serrano: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO)
Nature Communications, 2014, vol. 5, issue 1, 1-14
Abstract:
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.
Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5226
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DOI: 10.1038/ncomms5226
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