2014 Fiscal Year Final Research Report
Elucidation of Warburg effect in cancer with the next-generation proteomics
| Project/Area Number |
26640080
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2015-03-31
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| Keywords | がん / プロテオミクス / ワールブルグ効果 / 代謝 |
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| Outline of Final Research Achievements |
we developed a new platform (information-based MRM: iMRM) that allows genome-wide absolute quantification of the human proteome and is reliant on the production of ~18,000 recombinant proteins. We applied iMRM to delineate the metabolic landscape of human diploid fibroblasts. Oncogenic transformation of these cells gave rise to relatively small but global changes in metabolic pathways that account for aerobic glycolysis (Warburg effect) and increased rates of macromolecule synthesis. Modulation of metabolic enzyme expression revealed an unexpected functional interaction between glycolysis and the pentose phosphate pathway that facilitates nucleic acid synthesis. Furthermore, integration of proteomic and metabolomic data allowed construction of a mathematical model for identification of key enzymes responsible for the metabolic shift in cancer. Our results thus provide a global view of metabolic restructuring in cancer that underlies adaptation to a rapid growth state.
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| Free Research Field |
分子生物学
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