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<title lang=en>The environmental carcinogen benzo[a]pyrene induces a Warburg-like metabolic reprogramming dependent on NHE1 and associated with cell survival</title>
<creator>Hardonnière, Kevin</creator>
<creator>Saunier, Elise</creator>
<creator>Lemarié, Anthony</creator>
<creator>Fernier, Morgane</creator>
<creator>Gallais, Isabelle</creator>
<creator>Helies-Toussaint, Cecile</creator>
<creator>Mograbi, Baharia</creator>
<creator>Antonio, Samantha</creator>
<creator>Bénit, Paule</creator>
<creator>Rustin, Pierre</creator>
<creator>Janin, Maxime</creator>
<creator>Habarou, Florence</creator>
<creator>Ottolenghi, Chris</creator>
<creator>Lavault, Marie-Thérèse</creator>
<creator>Benelli, Chantal</creator>
<creator>Sergent, Odile</creator>
<creator>Huc, Laurence</creator>
<creator>Bortoli, Sylvie</creator>
<creator>Lagadic-Gossmann, Dominique</creator>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Toxicologie, Pharmacologie et Signalisation Cellulaire (U1124) ; Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS)</contributor>
<contributor>Centre de Recherche en Cancérologie de Toulouse (CRCT) ; Université Paul Sabatier - Toulouse 3 (UPS) - CHU Toulouse [Toulouse] - Hôpital Purpan [Toulouse] - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<contributor>ToxAlim (ToxAlim) ; Institut National Polytechnique [Toulouse] (INP) - Institut National de la Recherche Agronomique (INRA) - Université Paul Sabatier - Toulouse 3 (UPS) - Ecole Nationale Vétérinaire de Toulouse</contributor>
<contributor>Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine) ; Université Nice Sophia Antipolis (UNS) ; Université Côte d'Azur (UCA) - Université Côte d'Azur (UCA)</contributor>
<contributor>Institut de Recherche sur le Cancer et le Vieillissement (IRCAN) ; Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Nice Sophia Antipolis (UNS) ; Université Côte d'Azur (UCA) - Université Côte d'Azur (UCA)</contributor>
<contributor>Neuroprotection du Cerveau en Développement (PROTECT) ; Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Robert Debré - Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<contributor>Faculté de Médecine ; Université Paris Diderot - Paris 7 (UPD7)</contributor>
<contributor>Paris-Centre de Recherche Cardiovasculaire (PARCC - U970) ; Hôpital Européen Georges Pompidou [APHP] (HEGP) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<contributor>Laboratoire de Biochimie Métabolique ; CHU Necker - Enfants Malades [AP-HP]</contributor>
<contributor>Plateforme microscopie électronique ; MRic Campus Santé, Rennes 1, France</contributor>
<contributor>French Ministry for Education and Research</contributor>
<contributor> Faculte des Sciences Pharmaceutiques et Biologiques de Rennes (University of Rennes 1)</contributor>
<contributor> Agence regionale sante Provence Alpes Cote d'Azur</contributor>
<contributor> Direction regionale de l'Environnement, de l'amenagement et du logement Provence Alpes Cote d'Azur [6.3.3.3, 6.3.3.4]</contributor>
<contributor> Universite Paris Descartes</contributor>
<contributor> Ligue contre le cancer [22,35,49,85]</contributor>
<contributor> French National Academy of Medicine</contributor>
<contributor> ANR [ANR-13-CESA-0009]</contributor>
<contributor> ITMO Cancer AVIESAN (National Alliance for Life Sciences and Health) within the framework of the Cancer Plan</contributor>
<contributor> Association for Cancer Research (ARC, CANC'AIR Genexposomic project)</contributor>
<contributor> Region Provence Alpes Cote d'Azur</contributor>
<description>International audience</description>
<source>ISSN: 2045-2322</source>
<source>EISSN: 2045-2322</source>
<source>Scientific Reports</source>
<publisher>Nature Publishing Group</publisher>
<identifier>hal-01359569</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/document</identifier>
<identifier>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569/file/The%20environmental%20carcinogen-CCBY%20%281%29.pdf</identifier>
<source>https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359569</source>
<source>Scientific Reports, Nature Publishing Group, 2016, 6, pp.30776. 〈10.1038/srep30776〉</source>
<identifier>DOI : 10.1038/srep30776</identifier>
<relation>info:eu-repo/semantics/altIdentifier/doi/10.1038/srep30776</relation>
<identifier>PUBMED : 27488617</identifier>
<relation>info:eu-repo/semantics/altIdentifier/pmid/27488617</relation>
<language>en</language>
<subject lang=en>complex ii</subject>
<subject lang=en> mitochondrial-function</subject>
<subject lang=en> apoptosis induction</subject>
<subject lang=en> respiratory-chain</subject>
<subject lang=en> oxidative stress</subject>
<subject lang=en> hepa1c1c7 cells</subject>
<subject lang=en> hexokinase-ii</subject>
<subject lang=en> atp synthase</subject>
<subject lang=en> hepg2 cells</subject>
<subject lang=en> kappa-b</subject>
<subject>[SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health</subject>
<subject>[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology</subject>
<subject>[SDV.CAN] Life Sciences [q-bio]/Cancer</subject>
<type>info:eu-repo/semantics/article</type>
<type>Journal articles</type>
<description lang=en>Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a human carcinogen according to the International Agency for Research on Cancer. In addition to triggering apoptotic signals, B[a]P may induce survival signals, both of which are likely to be involved in cancer promotion. We previously suggested that B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell survival signaling in rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing on energy metabolism. We found that B[a]P promoted a metabolic reprogramming. Cell respiration decreased and lactate production increased. These changes were associated with alterations in the tricarboxylic acid cycle which likely involve a dysfunction of the mitochondrial complex II. The glycolytic shift relied on activation of the Na+/H+ exchanger 1 (NHE1) and appeared to be a key feature in B[a]P-induced cell survival related to changes in cell phenotype (epithelial-to-mesenchymal transition and cell migration).</description>
<rights>http://creativecommons.org/licenses/by/</rights>
<date>2016</date>
<contributor>ANR-13-CESA-0009, STEATOX, Impact des agents chimiques environnementaux sur les mécanismes de progression pathologique de la stéatose hépatique(2013)</contributor>
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