title: NOX1 supports the metabolic remodeling of HepG2 cells.
abstract: NADPH oxidases are important sources of reactive oxygen species (ROS) which act as signaling molecules in the regulation of protein expression, cell proliferation, differentiation, migration and cell death. The NOX1 subunit is over-expressed in several cancers and NOX1 derived ROS have been repeatedly linked with tumorigenesis and tumor progression although underlying pathways are ill defined. We engineered NOX1-depleted HepG2 hepatoblastoma cells and employed differential display 2DE experiments in order to investigate changes in NOX1-dependent protein expression profiles. A total of 17 protein functions were identified to be dysregulated in NOX1-depleted cells. The proteomic results support a connection between NOX1 and the Warburg effect and a role for NOX in the regulation of glucose and glutamine metabolism as well as of lipid, protein and nucleotide synthesis in hepatic tumor cells. Metabolic remodeling is a common feature of tumor cells and understanding the underlying mechanisms is essential for the development of new cancer treatments. Our results reveal a manifold involvement of NOX1 in the metabolic remodeling of hepatoblastoma cells towards a sustained production of building blocks required to maintain a high proliferative rate, thus rendering NOX1 a potential target for cancer therapy.
authors: Experimental and Molecular Paediatric Cardiology, German Heart Centre Munich at the Technical University Munich, Lazarettstr. 36, Munich, Germany.
authors: Katharina
authors: K
authors: Bertram
authors: Experimental and Molecular Paediatric Cardiology, German Heart Centre Munich at the Technical University Munich, Lazarettstr. 36, Munich, Germany.
authors: Cristina-Maria
authors: CM
authors: Valcu
authors: Experimental and Molecular Paediatric Cardiology, German Heart Centre Munich at the Technical University Munich, Lazarettstr. 36, Munich, Germany.
authors: Michael
authors: M
authors: Weitnauer
authors: Chemistry Department-Mass Spectrometry, Philipps-University Marburg, Hans-Meerwein-Strasse, Marburg, Germany.
authors: Uwe
authors: U
authors: Linne
authors: Experimental and Molecular Paediatric Cardiology, German Heart Centre Munich at the Technical University Munich, Lazarettstr. 36, Munich, Germany.
authors: Agnes
authors: A
authors: Görlach
mesh_terms: D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism; D053858:Metabolic Networks and Pathways; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation
chemical_list: D011506:Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D005973:Glutamine; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; D005947:Glucose