Biological roles of ALK-binding molecules in neuroblastoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 26290043
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Kitasato 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