| Budget Amount *help |
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2015: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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| Outline of Final Research Achievements |
Arf6 and AMAP1 are highly expressed in different cancers including breast cancer, and mediate integrin recycling to plasma membrane to promote cancer invasion and metastasis. On the other hand, signaling downstream of integrins is well known to contribute to resistance to radiation and chemotherapy. In this study, we have shown that reduction of the integrin signaling by blockade of the Arf6-AMAP1 pathway inhibits intracellular mitochondrial distribution, resulting in aggregated mitochondria around the nucleus, which induces amplification of the reactive oxygen species (ROS) produced by ionizing radiation. We have also revealed molecules involved in the regulation of mitochondrial distribution downstream of integrins, and how they interact with each other. Further analyses may lead to the establishment of a new modality for radio-sensitization, which is based on the ROS amplification mediated by mitochondrial aggregation.
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