| Budget Amount *help |
¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Research Abstract |
To elucidate the role of anaplastic lymphoma kinase (ALK) in oncogenesis of neuroblastoma, phosphotyrosine-containing proteins associated with ALK were investigated. Flotillin-1 (FLOT1), a plasma membrane protein involved in endocytosis, was identified as a binding partner of ALK. Knockdown of FLOT1 in neuroblastoma cells caused dissociation of ALK from endosomes along with membrane accumulation of ALK, which resulted in activation of ALK and downstream signals. Suppression of FLOT1 expression also enhanced oncogenic properties of neuroblastoma cells both in vitro and in vivo. On the other hand, oncogenic ALK mutants showed less binding affinity to FLOT1. Lower expression levels of FLOT1 were observed in highly malignant subgroups of human neuroblastoma tissues. Taken together, it was suggested that decreased levels of FLOT1 or defects in binding affinity between ALK mutants and FLOT1 may cause malignant phenotypes of neuroblastoma through the activation of ALK signaling.
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