title: Cutting Edge: NANOG Activates Autophagy under Hypoxic Stress by Binding to BNIP3L Promoter.
abstract: Hypoxia upregulates the core pluripotency factors NANOG, SOX2, and OCT4, associated with tumor aggressiveness and resistance to conventional anticancer treatments. We have previously reported that hypoxia-induced NANOG contributed in vitro to tumor cell resistance to autologous-specific CTL and in vivo to the in situ recruitment of immune-suppressive cells. In this study, we investigated the mechanisms underlying NANOG-mediated tumor cell resistance to specific lysis under hypoxia. We demonstrated the tumor-promoting effect of hypoxia on tumor initiation into immunodeficient mice using human non-small lung carcinoma cells. We next showed a link between NANOG and autophagy activation under hypoxia because inhibition of NANOG decreased autophagy in tumor cells. Chromatin immunoprecipitation and luciferase reporter assays revealed a direct binding of NANOG to a transcriptionally active site in a BNIP3L enhancer sequence. These data establish a new link between the pluripotency factor NANOG and autophagy involved in resistance to CTL under hypoxia.
authors.affiliation: INSERM UMR1186, Immunologie Intégrative des Tumeurs, Equipe Labellisée Ligue contre le Cancer, Institut Gustave Roussy, 94800 Villejuif, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Hasmim
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health, 1526 Luxembourg City, Luxembourg.
authors.forename: Bassam
authors.identifier: 0000-0002-9763-0943
authors.initials: B
authors.lastname: Janji
authors.affiliation: INSERM UMR1186, Immunologie Intégrative des Tumeurs, Equipe Labellisée Ligue contre le Cancer, Institut Gustave Roussy, 94800 Villejuif, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khaled
authors.affiliation: INSERM UMR1186, Immunologie Intégrative des Tumeurs, Equipe Labellisée Ligue contre le Cancer, Institut Gustave Roussy, 94800 Villejuif, France.
authors.forename: Muhammad Zaeem
authors.initials: MZ
authors.lastname: Noman
authors.affiliation: INSERM U1009, Institut Gustave Roussy, Institut Fédératif de Recherche 54, 94800 Villejuif, France; and.
authors.forename: Fawzia
authors.identifier: 0000-0002-4247-5421
authors.initials: F
authors.lastname: Louache
authors.affiliation: NF-κB, Differentiation, and Cancer, Paris Descartes University, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Bordereaux
authors.affiliation: INSERM UMR1186, Immunologie Intégrative des Tumeurs, Equipe Labellisée Ligue contre le Cancer, Institut Gustave Roussy, 94800 Villejuif, France.
authors.forename: Abdou
authors.initials: A
authors.lastname: Abderamane
authors.affiliation: NF-κB, Differentiation, and Cancer, Paris Descartes University, Sorbonne Paris Cité, 75006 Paris, France.
authors.forename: Veronique
authors.identifier: 0000-0002-4090-718X
authors.initials: V
authors.lastname: Baud
authors.affiliation: INSERM UMR1186, Immunologie Intégrative des Tumeurs, Equipe Labellisée Ligue contre le Cancer, Institut Gustave Roussy, 94800 Villejuif, France.
authors.forename: Fathia
authors.initials: F
authors.lastname: Mami-Chouaib
authors.affiliation: INSERM UMR1186, Immunologie Intégrative des Tumeurs, Equipe Labellisée Ligue contre le Cancer, Institut Gustave Roussy, 94800 Villejuif, France; salem.chouaib@gustaveroussy.fr.
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
mesh_terms: D000818:Animals; D001343:Autophagy; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000071317:Nanog Homeobox Protein / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D000071317:Nanog Homeobox Protein; C501741:Nix protein, mouse