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2017 Fiscal Year Final Research Report

Biological roles of ALK-binding molecules in neuroblastoma

Research Project

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Project/Area Number 26290043
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Tumor biology
Research InstitutionKitasato University (2015-2017)
National Cancer Center Japan (2014)

Principal Investigator

Sakai Ryuichi  北里大学, 医学部, 教授 (40215603)

Co-Investigator(Kenkyū-buntansha) 白木原 琢哉  北里大学, 医学部, 助教 (30548756)
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
Project Period (FY) 2014-04-01 – 2018-03-31
Keywords神経芽腫 / SHP2 / ALK
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.

Free Research Field

細胞内シグナル伝達

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Published: 2019-03-29  

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