title: Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia.
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.
authors: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors: Daniela
authors: D
authors: Piazzolla
authors: 1] Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain [2].
authors: Adelaida R
authors: AR
authors: Palla
authors: 1] Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain [2].
authors: Cristina
authors: C
authors: Pantoja
authors: Histopathology Core Unit, CNIO, Madrid 28029, Spain.
authors: Marta
authors: M
authors: Cañamero
authors: Cell Division and Cancer Group, CNIO, Madrid 28029, Spain.
authors: Ignacio Perez
authors: IP
authors: de Castro
authors: Transgenic Mice Core Unit, CNIO, Madrid 28029, Spain.
authors: Sagrario
authors: S
authors: Ortega
authors: Bioinformatics Unit, CNIO, Madrid 28029, Spain.
authors: Gonzalo
authors: G
authors: Gómez-López
authors: Genomics Core Unit, CNIO, Madrid 28029, Spain.
authors: Orlando
authors: O
authors: Dominguez
authors: Confocal Microscopy Core Unit, CNIO, Madrid 28029, Spain.
authors: Diego
authors: D
authors: Megías
authors: Monoclonal Antibodies Core Unit, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors: Giovanna
authors: G
authors: Roncador
authors: Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Madrid 28040, Spain.
authors: Jose L
authors: JL
authors: Luque-Garcia
authors: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
authors: Beatriz
authors: B
authors: Fernandez-Tresguerres
authors: Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain.
authors: Agustin F
authors: AF
authors: Fernandez
authors: 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.
authors: Mario F
authors: MF
authors: Fraga
authors: Department of Pathology, University College Hospital, London NW1 2BU, UK.
authors: Manuel
authors: M
authors: Rodriguez-Justo
authors: Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain.
authors: Miguel
authors: M
authors: Manzanares
authors: CIC bioGUNE, Bizkaia Technology Park, Derio 48160 and Ikerbasque, Basque Foundation for Science, Bilbao 48011, Spain.
authors: Marta
authors: M
authors: Sánchez-Carbayo
authors: Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo 33006, Spain.
authors: Juana María
authors: JM
authors: García-Pedrero
authors: Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo 33006, Spain.
authors: Juan P
authors: JP
authors: Rodrigo
authors: Cell Division and Cancer Group, CNIO, Madrid 28029, Spain.
authors: Marcos
authors: M
authors: Malumbres
authors: Tumour Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
authors: Manuel
authors: M
authors: Serrano
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage; D049109:Cell Proliferation; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis; D000071317:Nanog Homeobox Protein; D011401:Promoter Regions, Genetic; D013045:Species Specificity
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; C576918:Aurka protein, mouse; D064096:Aurora Kinase A