| Project/Area Number |
18K16094
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | University of Miyazaki |
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Principal Investigator |
Saito Yusuke 宮崎大学, 医学部, 講師 (20585674)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | がん代謝 / 白血病 / 解糖系 / 急性白血病 |
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| Outline of Final Research Achievements |
Proliferating leukemic cells consume substantial glucose, which lead to glucose insufficiency in bone marrow. However, leukemia cells can survive under low glucose conditions. In this study, we aim to identify a metabolic pathway of leukemia cells to provide the energy source for glycolysis under low glucose conditions. Our results showed that fructose and mannose are used as the energy source for glycolysis. Cells uptake mannose via the same transporter as glucose and covert mannose to glucose by Mannose-6-phosphate isomerase (MPI) for glycolysis. We established leukemia cell lines with a reduced MPI expression and showed that cell growth is suppressed and mannose reduces glycolysis activity in MPI knockdown cells. Surprisingly, mannose inhibited the regular metabolic pathway of glucose in MPI knockdown cells. The mannose metabolic pathway can be the therapeutic targets for leukemia.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで白血病細胞が骨髄でのグルコース飢餓状態においてどのように解糖系を維持しているのか明らかになっていなかった。白血病細胞がグルコース以外の糖質としてマンノースを解糖系エネルギー源として利用することを始めて明らかにした。MPI高発現は白血病の予後不良因子であり、マンノース-解糖系代謝は白血病の新規治療標的となり得る。今後の展開として、MPI低発現のがん細胞に対してはグルコースに変えてマンノースを糖質として摂取する、MPI高発現のがん細胞ではMPI阻害とマンノース負荷を併用することでがん増殖を抑制するがん代謝食事療法の開発に繋げる。
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