title: The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase.
abstract: We report that the mitochondrial chaperone TRAP1, which is induced in most tumor types, is required for neoplastic growth and confers transforming potential to noncancerous cells. TRAP1 binds to and inhibits succinate dehydrogenase (SDH), the complex II of the respiratory chain. The respiratory downregulation elicited by TRAP1 interaction with SDH promotes tumorigenesis by priming the succinate-dependent stabilization of the proneoplastic transcription factor HIF1α independently of hypoxic conditions. These findings provide a mechanistic clue to explain the switch to aerobic glycolysis of tumors and identify TRAP1 as a promising antineoplastic target.
authors.affiliation: CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Sciacovelli
authors.affiliation: CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Guzzo
authors.affiliation: Molecular Biotechnology Centre, Department of Genetics, Biology and Biochemistry, University of Torino, 10125 Torino, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Morello
authors.affiliation: Cancer Research United Kingdom, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Frezza
authors.affiliation: Cancer Research United Kingdom, The Beatson Institute for Cancer Research, Glasgow G61 1BD, UK; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G61 1BD, UK.
authors.forename: Liang
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, 35121 Padova, Italy.
authors.forename: Nazarena
authors.initials: N
authors.lastname: Nannini
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, 35121 Padova, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Calabrese
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, 80131 Napoli, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Laudiero
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies, University of Napoli Federico II, 80131 Napoli, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Esposito
authors.affiliation: Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Landriscina
authors.affiliation: Molecular Biotechnology Centre, Department of Genetics, Biology and Biochemistry, University of Torino, 10125 Torino, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Defilippi
authors.affiliation: CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy. Electronic address: bernardi@bio.unipd.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
authors.affiliation: CNR Institute of Neuroscience, Department of Biomedical Sciences and Venetian Institute of Molecular Medicine, University of Padova, 35121 Padova, Italy. Electronic address: rasola@bio.unipd.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rasola
mesh_terms: D063646:Carcinogenesis / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D010101:Oxygen Consumption; D034622:RNA Interference; D034741:RNA, Small Interfering; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*
chemical_list: C497442:HIF1A protein, human; D018841:HSP90 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; C092306:TRAP1 protein, human; D013385:Succinate Dehydrogenase