2013 Fiscal Year Final Research Report

The elucidation of the new mechanism of melanoma cell movement

Research Project

Project/Area Number	24791165
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Dermatology
Research Institution	Sapporo Medical University
Principal Investigator	KUNIMOTO Risa 札幌医科大学, 医学部, 助教 (20468094)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	SIRT1 / メラノーマ / 細胞移動 / 癌転移
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.