2013 Fiscal Year Final Research Report
Analysis of mediators of ALK signaling activated in neuroblastoma
| Project/Area Number |
23300353
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
SAKAI RYUICHI 独立行政法人国立がん研究センター, 研究所, 分野長 (40215603)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | ALK / 神経芽腫 / チロシンリン酸化 / シグナル伝達 / 質量分析 |
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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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[Journal Article] Flotillin-1 regulates oncogenic signaling in neuroblastoma cells by regulating ALK membrane association2014
Author(s)
Tomiyama A, Uekita T, Kamata R, Sasaki K, Takita J, Ohira M, Nakagawara A, Kitanaka C, Mori K, Yamaguchi H, Sakai R
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Journal Title
Cancer Res
Volume: (in press)
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[Journal Article] Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer2013
Author(s)
Kasuga M, Ueki K, Tajima N, Noda M, Ohashi K, Noto H, Goto A, Ogawa W, Sakai R, Tsugane S, Hamajima N, Nakagama H, Tajima K, Miyazono K, Imai K
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Journal Title
Cancer Sci
Volume: 104
Pages: 965-976
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[Journal Article] Cancer susceptibility polymorphism of p53 at codon 72 affects phosphorylation and degradation of p53 protein2011
Author(s)
Ozeki C, Sawai Y, Shibata T, Kohno T, Okamoto K, Yokota J, Tashiro F, Tanuma S, Sakai R, Kawase T, Kitabayashi I, Taya Y & Ohki R
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Journal Title
J Biol Chem
Volume: 286
Pages: 18251-18260
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