| Budget Amount *help |
¥43,000,000 (Direct Cost: ¥43,000,000)
Fiscal Year 2009: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2008: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2007: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2006: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 2005: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Research Abstract |
Molecular and biochemical mechanisms of adaptive responses of cancer cells to deprivation of both oxygen and nutrient, which mimics tumor microenvironment of hypovascular tumors have been analyzed. In this series of experiments we have found following. 1)Tumor cells especially those from hypovascular tumor show resistance to hypoglycemia and even normal cells can be converted resistant to glucose deprivation by hypoxic condition. 2)AMPK AKT and AMPK-related kinases are involved in the response. 3)These molecules are involved in invasion and metastasis. 4)Under deprivation of nutrient and oxygen, autophagy is involved in cell survival. 5)Anaerobic energy production through fumarate respiration was found to be induced and operated by deprivation of both oxygen and glucose. 6)The metabolomic analysis of human cancer tissues strongly suggested anaerobic energy production through fumarate respiration. The present results opened a way to develop a novel strategy to treat cancer by targeting cancer cells' adaptation to their microenvironment.
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