title: (1)H NMR metabolomics analysis of renal cell carcinoma cells: Effect of VHL inactivation on metabolism.
abstract: Von Hippel-Lindau (VHL) is an onco-suppressor involved in oxygen and energy-dependent promotion of protein ubiquitination and proteosomal degradation. Loss of function mutations of VHL (VHL-cells) result in organ specific cancers with the best studied example in renal cell carcinomas. VHL has a well-established role in deactivation of hypoxia-inducible factor (HIF-1) and in regulation of PI3K/AKT/mTOR activity. Cell culture metabolomics analysis was utilized to determined effect of VHL and HIF-1α or HIF-2α on metabolism of renal cell carcinomas (RCC). RCC cells were stably transfected with VHL or shRNA designed to silence HIF-1α or HIF-2α genes. Obtained metabolic data was analysed qualitatively, searching for overall effects on metabolism as well as quantitatively, using methods developed in our group in order to determine specific metabolic changes. Analysis of the effect of VHL and HIF silencing on cellular metabolic footprints and fingerprints provided information about the metabolic pathways affected by VHL through HIF function as well as independently of HIF. Through correlation network analysis as well as statistical analysis of significant metabolic changes we have determined effects of VHL and HIF on energy production, amino acid metabolism, choline metabolism as well as cell regulation and signaling. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors.
authors.affiliation: National Research Council of Canada, Moncton, NB, Canada.|Department of Chemistry and Biochemistry, Université De Moncton, Moncton, NB, Canada.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Cuperlovic-Culf
authors.affiliation: Department of Chemistry and Biochemistry, Université De Moncton, Moncton, NB, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Cormier
authors.affiliation: Department of Chemistry and Biochemistry, Université De Moncton, Moncton, NB, Canada.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Touaibia
authors.affiliation: Department of Chemistry and Biochemistry, Université De Moncton, Moncton, NB, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Reyjal
authors.affiliation: Department of Chemistry and Biochemistry, Université De Moncton, Moncton, NB, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Robichaud
authors.affiliation: Department of Chemistry and Biochemistry, Université De Moncton, Moncton, NB, Canada.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Belbraouet
authors.affiliation: Department of Chemistry and Biochemistry, Université De Moncton, Moncton, NB, Canada.|Atlantic Cancer Research Institute, Moncton, NB, Canada.
authors.forename: Sandra
authors.initials: S
authors.lastname: Turcotte
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007680:Kidney Neoplasms / Q000378:metabolism*; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D009154:Mutation; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: HIF; NMR metabolomics; RCC; VHL; cancer metabolism; hypoxia; renal cancer