Comprehensive quantification and visualization of energy metabolism in cell competition between dying and living cells.
Project/Area Number |
23657150
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Developmental biology
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Research Institution | Waseda University |
Principal Investigator |
MATSUDA Nanami (Senoo-Matsuda Nanami) 早稲田大学, 先端科学・健康医療融合研究機構, 准教授 (70360641)
|
Co-Investigator(Renkei-kenkyūsha) |
IMAMURA Hiromi 京都大学, 大学院・生命科学研究科, 准教授 (20422545)
|
Project Period (FY) |
2011 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 細胞競合 / エネルギー代謝 / Myc / p53 / ショウジョウバエ / メタボローム / 可視化 / 細胞間相互作用 |
Research Abstract |
When growing in mosaic tissues, cells with extra Drosophila Myc expression exhibit "super-competitor" behavior that enables them to kill their wildtype neighbors and overtake the tissue. Here we have explored the basis for super-competitor status of dMyc-expressing cells during cell competition. We find that expression of dMyc, like c-myc, induces metabolic reprogramming resembling the Warburg effect, which is balanced by homeostatic metabolic functions of p53. However, in mosaics, confrontation between dMyc-expressing and wildtype cells heightens the metabolism of dMyc cells and leads p53-dependency for their clonal expansion, viability, and super-competitor status. We propose that confrontation with WT cells increases the fitness of dMyc cells and that p53 functions as a sensor of these fitness differences. Oncogenic activation can lead to metabolic changes that are physiologically important for tumor progression, and our data suggest that confrontation of incipient tumor cells and non-tumorigenic neighbors within a tissue may actually promote tumorigenesis.
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Report
(3 results)
Research Products
(18 results)