title: The pluripotency factor NANOG promotes the formation of squamous cell carcinomas.
abstract: NANOG is a key pluripotency factor in embryonic stem cells that is frequently expressed in squamous cell carcinomas (SCCs). However, a direct link between NANOG and SCCs remains to be established. Here, we show that inducible overexpression of NANOG in mouse skin epithelia favours the malignant conversion of skin papillomas induced by chemical carcinogenesis, leading to increased SCC formation. Gene expression analyses in pre-malignant skin indicate that NANOG induces genes associated to epithelial-mesenchymal transition (EMT). Some of these genes are directly activated by NANOG, including EMT-associated genes Zeb1, Zeb2, Twist1, Prrx1 and miR-21. Finally, endogenous NANOG binds to the promoters of theses genes in human SCC cells and, moreover, NANOG induces EMT features in primary keratinocytes. These results provide in vivo evidence for the oncogenic role of NANOG in squamous cell carcinomas.
authors.forename: Adelaida R
authors.initials: AR
authors.lastname: Palla
authors.forename: Daniela
authors.initials: D
authors.lastname: Piazzolla
authors.forename: Noelia
authors.initials: N
authors.lastname: Alcazar
authors.forename: Marta
authors.initials: M
authors.lastname: Cañamero
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Graña
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Gómez-López
authors.forename: Orlando
authors.initials: O
authors.lastname: Dominguez
authors.affiliation: 1] Molecular Oncology Unit, CIEMAT, Madrid 28040, Spain [2] Oncogenomic Unit, Institute of Biomedical Research, University Hospital "12 de Octubre", Madrid 28040, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Dueñas
authors.affiliation: 1] Molecular Oncology Unit, CIEMAT, Madrid 28040, Spain [2] Oncogenomic Unit, Institute of Biomedical Research, University Hospital "12 de Octubre", Madrid 28040, Spain.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Paramio
authors.forename: Manuel
authors.initials: M
authors.lastname: Serrano
mesh_terms: D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000473:pathology; D010212:Papilloma / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D017423:Sequence Analysis, RNA; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse