title: Energy management by enhanced glycolysis in G1-phase in human colon cancer cells in vitro and in vivo.
abstract: Activation of aerobic glycolysis in cancer cells is well known as the Warburg effect, although its relation to cell- cycle progression remains unknown. In this study, human colon cancer cells were labeled with a cell-cycle phase-dependent fluorescent marker Fucci to distinguish cells in G1-phase and those in S + G2/M phases. Fucci-labeled cells served as splenic xenograft transplants in super-immunodeficient NOG mice and exhibited multiple metastases in the livers, frozen sections of which were analyzed by semiquantitative microscopic imaging mass spectrometry. Results showed that cells in G1-phase exhibited higher concentrations of ATP, NADH, and UDP-N-acetylglucosamine than those in S and G2-M phases, suggesting accelerated glycolysis in G1-phase cells in vivo. Quantitative determination of metabolites in cells synchronized in S, G2-M, and G1 phases suggested that efflux of lactate was elevated significantly in G1-phase. By contrast, ATP production in G2-M was highly dependent on mitochondrial respiration, whereas cells in S-phase mostly exhibited an intermediary energy metabolism between G1 and G2-M phases. Isogenic cells carrying a p53-null mutation appeared more active in glycolysis throughout the cell cycle than wild-type cells. Thus, as the cell cycle progressed from G2-M to G1 phases, the dependency of energy production on glycolysis was increased while the mitochondrial energy production was reciprocally decreased.
  
  
  CONCLUSIONS
  These results shed light on distinct features of the phase-specific phenotypes of metabolic systems in cancer cells.
authors.affiliation: Department of Biochemistry, School of Medicine, Keio University, and Leader, JST ERATO Suematsu Gas Biology Project, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. gasbiology@z6.keio.jp.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Mukai
authors.forename: Takako
authors.initials: T
authors.lastname: Hishiki
authors.forename: Akiko
authors.initials: A
authors.lastname: Kubo
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Ohmura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsuura
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nagahata
authors.forename: Noriyo
authors.initials: N
authors.lastname: Hayakawa
authors.forename: Takehiro
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Ryo
authors.initials: R
authors.lastname: Fukuda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Yoji Andrew
authors.initials: YA
authors.lastname: Minamishima
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004734:Energy Metabolism; D016193:G1 Phase; D016195:G2 Phase; D006019:Glycolysis; D045325:HCT116 Cells; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009368:Neoplasm Transplantation; D010085:Oxidative Phosphorylation; D016196:S Phase
chemical_list: D000255:Adenosine Triphosphate