| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
Most malignant melanoma cases carry BRAF-active mutations, therefore the BRAF inhibitor is effective in treatments. But drug resistance eventually develops. This study examined whether changes in the integrin-survival signaling affected by alterations in cell surface glycosylation and in phospholipids in outer leaflet of plasma membranes involve in the BRAF inhibitor resistance of melanoma cells. Our results showed that CD63, an integrin signaling-associated molecule, was highly modified with polylactosamine sugar chains upon the BRAF inhibitor treatments, resulting in upregulated expression of cell surface CD63 and increases in the BRAF inhibitor susceptibility. We detected appearance of lipids, which are primarily located in inner leaflet of plasma membrane, in outer leaflet of melanoma cells, and exhibited its involvement in cell adhesion. These results may lead to develop a novel tool to treat drug-resistant malignant melanoma.
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