| Project/Area Number |
26290043
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kitasato University (2015-2017)
National Cancer Center Japan (2014) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
白木原 琢哉 北里大学, 医学部, 助教 (30548756)
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| Research Collaborator |
YAMAGUCHI Hideki 公立財団法人佐々木研究所, 腫瘍細胞研究部, 部長
Tomiyama Arata 防衛医科大学校, 脳神経外科, 講師
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
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| Keywords | 神経芽腫 / SHP2 / ALK / チロシンキナーゼ / チロシンリン酸化 / Flotillin / Shp2 / 癌 / 細胞・組織 / 分子標的治療薬 / 薬剤感受性 / ＡＬＫ / ＳＨＰ２ / Flotillin-1 |
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| Outline of Final Research Achievements |
By the screening of phosphotyrosine-containing proteins associated with ALK in neuroblastoma cells, we identified SHP2 as one of the binding partners of ALK. Immunoprecipitation study revealed binding of SHP2 with ALK by ALK activity-dependent manner, and knockdown of ALK or inhibition of kinase activity of ALK by ALK inhibitors suppressed phosphorylation of SHP2 at Tyr540 and Tyr580 in NB-39-nu neuroblastoma cells which have ALK addiction. In addition, knockdown of ALK-binding docking protein ShcC resulted in decrease of ALK-SHP2 interaction. On the other hands, treatment of SHP2 inhibitor PHPS1 or knockdown of SHP2 resulted in down-regulation of ERK1/2 activation, proliferation and migration of NB-39-nu cell. However, phosphorylation of ALK was up-regulated by inhibition or knockdown of SHP2. From these results, very complicated interplay between ALK and SHP2 during the regulation of oncogenesis of the neuroblastoma cells is suggested.
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