title: Frequent alteration of the protein synthesis of enzymes for glucose metabolism in hepatocellular carcinomas.
abstract: BACKGROUND
  Cancer cells show enhanced glycolysis and inhibition of oxidative phosphorylation, even in the presence of sufficient oxygen (aerobic glycolysis). Glycolysis is much less efficient for energy production than oxidative phosphorylation, and the reason why cancer cells selectively use glycolysis remains unclear.
  
  
  METHODS
  Biospecimens were collected from 45 hepatocellular carcinoma patients. Protein samples were prepared through subcellular localization or whole-cell lysis. Protein synthesis was measured by SDS-PAGE and immunoblotting. mRNA transcription was measured using quantitative RT-PCR. Statistical correlation among immunoblotting data and clinicolaboratory factors were analyzed using SPSS.
  
  
  RESULTS
  Enzymes for oxidative phosphorylation (SDHA and SDHB) were frequently decreased (56 and 48 % of patients, respectively) in hepatocellular carcinomas. The lowered amount of the SDH protein complex was rarely accompanied by stabilization of HIF1α and subsequent activation of the hypoxia response. On the other hand, protein synthesis of G6PD and TKT, enzymes critical for pentose phosphate pathway (PPP), was increased (in 45 and 55 % of patients, respectively), while that of ALDOA, an enzyme for mainstream glycolysis, was eliminated (in 55 % of patients). Alteration of protein synthesis was correlated with gene expression for G6PD and TKT, but not for TKTL1, ALDOA, SDHA or SDHB. Augmented transcription and synthesis of PPP enzymes were accompanied by nuclear accumulation of NRF2.
  
  
  CONCLUSIONS
  Hepatocellular carcinomas divert glucose metabolism to the anabolic shunt by activating transcription factor NRF2.
authors.affiliation: Second Department of Surgery, Dokkyo Medical University, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi, 321-0293, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Inoue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hachiya
authors.forename: Norisuke
authors.initials: N
authors.lastname: Shibuya
authors.forename: Mitsugi
authors.initials: M
authors.lastname: Shimoda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kubota
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010427:Pentose Phosphate Pathway / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012333:RNA, Messenger; D005947:Glucose