RRC ID 44469
著者 Bao Y, Mukai K, Hishiki T, Kubo A, Ohmura M, Sugiura Y, Matsuura T, Nagahata Y, Hayakawa N, Yamamoto T, Fukuda R, Saya H, Suematsu M, Minamishima YA.
タイトル Energy management by enhanced glycolysis in G1-phase in human colon cancer cells in vitro and in vivo.
ジャーナル Mol Cancer Res
Abstract UNLABELLED: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.
IMPLICATIONS:These results shed light on distinct features of the phase-specific phenotypes of metabolic systems in cancer cells.
巻・号 11(9)
ページ 973-85
公開日 2013-9-1
DOI 10.1158/1541-7786.MCR-12-0669-T
PII 1541-7786.MCR-12-0669-T
PMID 23741060
MeSH Adenosine Triphosphate / metabolism Animals Cell Line Colonic Neoplasms / metabolism* Colonic Neoplasms / pathology* Energy Metabolism* G1 Phase* G2 Phase Glycolysis* HCT116 Cells Heterografts Humans Liver Neoplasms / metabolism Liver Neoplasms / secondary Mice Mitochondria / metabolism Neoplasm Transplantation Oxidative Phosphorylation S Phase
IF 4.63
引用数 38
WOS 分野 ONCOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 293T(RCB2202)