| Budget Amount *help |
¥167,830,000 (Direct Cost: ¥129,100,000、Indirect Cost: ¥38,730,000)
Fiscal Year 2015: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
Fiscal Year 2014: ¥31,070,000 (Direct Cost: ¥23,900,000、Indirect Cost: ¥7,170,000)
Fiscal Year 2013: ¥32,890,000 (Direct Cost: ¥25,300,000、Indirect Cost: ¥7,590,000)
Fiscal Year 2012: ¥32,500,000 (Direct Cost: ¥25,000,000、Indirect Cost: ¥7,500,000)
Fiscal Year 2011: ¥40,300,000 (Direct Cost: ¥31,000,000、Indirect Cost: ¥9,300,000)
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| Outline of Final Research Achievements |
Drug resistance and high motility of cancer are central to malignancies. These phenotypes often emerge coupled with the mesenchymal programs. Arf6 and its effector AMAP1 are often overexpressed in various cancers, and promote invasion and metastasis. We first found that AMAP1 binds to EPB41L5, which is normally expressed in mesenchymes to promote focal adhesion dynamics. Thus, the Arf6 pathway appears to be a cancer-specific mesenchymal pathway. Moreover, the mevalonate pathway (MVP) was essential to Arf6 activation, via geranylgeranyl transferase-II and its substrate Rab11b. Mutant-p53s promoted Arf6 activation, via enhancing MVP. Besides receptor tyrosine kinases, G-protein-coupled receptor for LPA also directly activated Arf6. We finally demonstrated that the overexpressed Arf6 pathway promotes drug resistance. Our results showed that the Arf6-based pathway is critical to cancer malignancies and drug resistance, and provide excellent therapeutic opportunities.
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