| Budget Amount *help |
¥8,810,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2006: ¥4,000,000 (Direct Cost: ¥4,000,000)
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| Research Abstract |
Cancer cells have a propensity to produce energy (=ATP) in an anaerobic manner even in the presence of ample oxygen, which is termed Warburg effect Warburg effect is thus a common phenotype of cancer cells and forms a basis for cancer detection by 18-fluorodeoxyglucose positron emission tomography ([^<18>F]FDG-PET) scans. However, why cancer cells choose to rely heavily on such an inefficient way of energy production (〜1/20 efficient compared to aerobic energy production) has remained a mystery for nearly 80 years since the discovery of Warburg effect In this research project, we have discovered that the aerobic energy metabolism, but not the anaerobic one, plays a pivotal role in the activation of Bax and Bak essential for mitochondria mediated cellular suicide (Tomiyama, et. Al., J Natl Cancer Inst 98: 1462-1473, 2006. This paper was selected as a "Research Highlight" in the December issue of Nature Reviews Cancer, 2006). Since cancer cells, unlike normal cells, are continuously exposed to various external and internal stimuli that cause them to commit suicide, cancer cells need to actively avoid suicide to survive and grow. Thus, with our discovery, the "seemingly absurd energy metabolism" of cancer cells can now be viewed as a "crafty strategy" to avoid suicide commitment at the cost of energy production efficiency.
Another important implication of our findings in light of cancer therapeutics is that, if we can shift the metabolism of cancer cells from anaerobic to aerobic, then we can sensitize them to conventional cancer therapies, which often depend on the mitochondria mediated suicide mechanism for cell killing. In this respect, we have recently identified a natural compound that promotes aerobic metabolism of glioblastoma (GBM) cells. In the future project, we will be investigating whether this compound is useful in overcoming therapy resistance inherent to GBM cells.
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