論文 - 詳細
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) |