| Project/Area Number |
24791165
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
KUNIMOTO Risa 札幌医科大学, 医学部, 助教 (20468094)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | SIRT1 / メラノーマ / 細胞移動 / 癌転移 / Rac / ニコチンアミド / PIP3 / 日本 |
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| Research Abstract |
We found that melanoma cells expressed the NAD+-dependent deacetylase SIRT1 in the cytoplasm. Protrusion formation and migration of melanoma cells were inhibited by SIRT1 inhibitors or SIRT1 knockdown, whereas protrusion extension and migration were enhanced by SIRT1 activators. Serum or platelet derived growth factor (PDGF) recruited SIRT1 to the leading edge of the lamellipodia, a characteristic feature at the front of motile cells. SIRT1 inhibition prevented serum, PDGF, or dominant-active Rac1 (RacV12) from inducing lamellipodia in B16F1 melanoma cells. Serum or PDGF increased the phosphatidylinositol-3, 4, 5-trisphosphate level in the leading edge, and this increase was impaired by SIRT1 inhibition. The abdominal invasion of transplanted melanoma cells in mice was suppressed by the SIRT1 inhibitor nicotinamide and SIRT1 knockdown. therapy for melanoma.
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