| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
The hypoxic environment is substantial in solid tumors including gastric cancer (GC), where it accelerates their malignant behavior via HIF-1α pathway. Whereas, hypoxia is known to stimulate ROS production from mitochondrial complex III in the electron transport chain, and mitochondrial ROS (mtROS) stabilize HIF-1α leads to increased cancer aggressiveness.
Mitochondrial autophagy (mitophagy) is a selective form of autophagy and a critical step in excluding mitochondria damaged by stress, including hypoxia. Our data suggested that mtROS is accumulated under hypoxia in scirrhous GC cells due to impaired mitophagy, while mtROS is controlled at a low level through the normal mitophagy process in non-scirrhous GC cells.
This study demonstrated that the integrity of mitophagy determined the cancer aggressiveness of GC cells under hypoxic environment via the activation of the mtROS/HIF-1α interplay.
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