title: BRCA1 induces major energetic metabolism reprogramming in breast cancer cells.
abstract: The hypermetabolic nature of cancer cells and their increased reliance on "aerobic glycolysis", as originally described by Otto Warburg and colleagues, are considered metabolic hallmarks of cancer cells. BRCA1 is a major tumor suppressor in breast cancer and it was implicated in numerous pathways resulting in anticarcinogenic functions. The objective of our study was to address specific contributions of BRCA1 to the metabolic features of cancer cells, including the so-called "Warburg effect". To get a comprehensive approach of the role of BRCA1 in tumor cell metabolism, we performed a global transcriptional and metabolite profiling in a BRCA1-mutated breast cancer cell line transfected or not by wild-type BRCA1. This study revealed that BRCA1 induced numerous modifications of metabolism, including strong inhibition of glycolysis while TCA cycle and oxidative phosphorylation tended to be activated. Regulation of AKT by BRCA1 in both our cell model and BRCA1-mutated breast tumors was suggested to participate in the effect of BRCA1 on glycolysis. We could also show that BRCA1 induced a decrease of ketone bodies and free fatty acids, maybe consumed to supply Acetyl-CoA for TCA cycle. Finally increased activity of antioxidation pathways was observed in BRCA1-transfected cells, that could be a consequence of ROS production by activated oxidative phosphorylation. Our study suggests a new function for BRCA1 in cell metabolic regulation, globally resulting in reversion of the Warburg effect. This could represent a new mechanism by which BRCA1 may exert tumor suppressor function.
authors.affiliation: Jean Perrin Comprehensive Cancer Center and ERTICA EA4677 Research Team, University of Auvergne, Clermont-Ferrand, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Privat
authors.affiliation: Jean Perrin Comprehensive Cancer Center and ERTICA EA4677 Research Team, University of Auvergne, Clermont-Ferrand, France.
authors.forename: Nina
authors.initials: N
authors.lastname: Radosevic-Robin
authors.affiliation: Jean Perrin Comprehensive Cancer Center and ERTICA EA4677 Research Team, University of Auvergne, Clermont-Ferrand, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Aubel
authors.affiliation: Jean Perrin Comprehensive Cancer Center and ERTICA EA4677 Research Team, University of Auvergne, Clermont-Ferrand, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cayre
authors.affiliation: Jean Perrin Comprehensive Cancer Center and ERTICA EA4677 Research Team, University of Auvergne, Clermont-Ferrand, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Penault-Llorca
authors.affiliation: Laboratoire de biochimie médicale, Centre de biologie, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Marceau
authors.affiliation: Laboratoire de biochimie médicale, Centre de biologie, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Sapin
authors.affiliation: Jean Perrin Comprehensive Cancer Center and ERTICA EA4677 Research Team, University of Auvergne, Clermont-Ferrand, France.
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.affiliation: Jean Perrin Comprehensive Cancer Center and ERTICA EA4677 Research Team, University of Auvergne, Clermont-Ferrand, France; INRA, UMR 1019, UNH, Clermont-Ferrand, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Morvan
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002952:Citric Acid Cycle / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010085:Oxidative Phosphorylation
chemical_list: D019313:BRCA1 Protein; D009363:Neoplasm Proteins