title: Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype.
abstract: Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Kévin
authors.initials: K
authors.lastname: Hardonnière
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Fernier
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gallais
authors.affiliation: Institute of Research on Cancer and Ageing of Nice (IRCAN), INSERM U1081, CNRS UMR7284, Université de Nice-Sophia Antipolis, Faculté de Médecine, Centre Antoine Lacassagne, Nice, F-06107, France.
authors.forename: Baharia
authors.initials: B
authors.lastname: Mograbi
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Normand
authors.initials: N
authors.lastname: Podechard
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Le Ferrec
authors.affiliation: HBRU, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grova
authors.affiliation: HBRU, Luxembourg Institute of Health, 29, rue Henri Koch, L-4354, Esch-sur-Alzette, Luxembourg.
authors.forename: Brice
authors.initials: B
authors.lastname: Appenzeller
authors.affiliation: Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Burel
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Chevanne
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Sergent
authors.affiliation: INRA UMR 1331 ToxAlim, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Huc
authors.affiliation: INSERM UMR-S 1124, Université Paris Descartes, Centre Universitaire des Saint-Pères, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bortoli
authors.affiliation: Inserm U1085, Institut de Recherche en Santé, Environnement, Travail, Rennes, France. dominique.lagadic@univ-rennes1.fr.|Université de Rennes 1, Biosit UMS3080, 35043, Rennes Cédex, France. dominique.lagadic@univ-rennes1.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lagadic-Gossmann
mesh_terms: D000818:Animals; D017209:Apoptosis; D001564:Benzo(a)pyrene / Q000633:toxicity; D002274:Carcinogens, Environmental / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006019:Glycolysis; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D009374:Neoplasms, Experimental; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D000097795:ATPase Inhibitory Protein
chemical_list: D001564:Benzo(a)pyrene; D002274:Carcinogens, Environmental; D011084:Polycyclic Aromatic Hydrocarbons; D011506:Proteins; D018343:Receptors, Adrenergic, beta-2; D000097795:ATPase Inhibitory Protein; C553443:ADRB2 protein, human