Year-end Sale % OFF 
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.
Highlights
Reactive oxygen species (ROS) act as signaling molecules in the regulation of various physiological and pathological processes in almost all tissues [1]
We identified several protein functions dysregulated in the presence of reduced NOX1 levels, providing interesting indications regarding the involvement of NOX1 in the regulation of tumor cell metabolism
Our results suggest that HepG2 cells undergo a reprogramming of glutamine metabolism and NOX1 plays a role in this process by regulating the abundance of two of the key enzymes
Summary
Reactive oxygen species (ROS) act as signaling molecules in the regulation of various physiological and pathological processes in almost all tissues [1]. NADPH oxidases are important sources of ROS which are involved as second messengers in the regulation of gene expression as well as in cell proliferation, differentiation, migration and death. 7 homologous NADPH oxidase enzymes have been identified which mainly differ in the expression of the PLOS ONE | DOI:10.1371/journal.pone.0122002. NOX1 Supports the Metabolic Remodeling of HepG2 Cells 7 homologous NADPH oxidase enzymes have been identified which mainly differ in the expression of the PLOS ONE | DOI:10.1371/journal.pone.0122002 March 25, 2015
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
