Molecular basis of deregulated Wnt signaling in clinical colorectal cancer
| Project/Area Number |
18390363
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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 |
Digestive surgery
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| Research Institution | Kanazawa University |
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Principal Investigator |
MINAMOTO Toshinari Kanazawa University, がん研究所, 教授 (50239323)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Yutaka 千葉大学, 医学研究院, 教授 (10179541)
KAWAKAMI Kazuyuki 金沢大学, がん研究所, 准教授 (00293358)
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| Project Period (FY) |
2006 – 2008
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| Project Status |
Completed (Fiscal Year 2008)
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| Budget Amount *help |
¥17,690,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥2,790,000)
Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | 大腸がん / シグナル伝達 / Wnt / β-カテニン / GSK3β / β-catenin / β-TrCP / CRD-BP / 大腸癌 / β-カラニン |
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| Research Abstract |
Wnt経路の制御破綻が固有のがん化シグナルを誘発する仕組みと,それを修飾する分子細胞機構を解明するためにβ-catenin を中心とするがん化シグナルネットワークの概念を創出し, これを具現化する. 大腸がんのがん腫-宿主境界の微小環境におけるβ-catenin活性化の重要性, β-cateninとIκBα(inhibitor of NF-κB)に共通のユビキチン連結酵素β-TrCP(β-transducinrepeats-containing protein)の同定, これを転写後に制御するWnt経路の新規転写標的CRD-BP(coding region determinant-binding protein)の同定と,これらの分子の制御異常と病的作用を見出した. CRD-BPはc-mycやIGF-II(insulin-like growth factor-II)のRNAトランス因子であり, 大腸がんで複数の細胞増殖経路(Wnt, NF-κB, c-Myc, IGF-II)を機能的に結びつけるとことを明らかにした. その後, 現在までにCRD-BPを介するWntとHedgehog経路の交差応答や, 腸上皮細胞の極性輸送の制御異常にともなうE-cadherinの発現変化とβ-catenin活性化の関連について研究を進めている.
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Report
(4 results)
Research Products
(115 results)
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[Journal Article] The IL-6 family cytokine IL-11 regulates homeostatic epithelial cell turnover and promotes gastric tumor development2009
Author(s)
Howlett M, Giraud AS, Lescesen H, Jackson CB, Kalantzis A, van Driel IR, Robb L, Van der Hoek M, Minamoto T, Boussioutas A, Oshima H, Oshima M, Judd LM.
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Journal Title
Gastroenterology 136(3)
Pages: 967-77
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Peer Reviewed
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[Journal Article] Adjuvant immunochemotherapy with protein-bound polysaccharide K for colon cancer in relation to oncogenic β-catenin activation2007
Author(s)
Yamashita K, Ougolkov A, Nakazato H, Ito K, Ohashi Y, Kitakata H, Yasumoto K, Omote K, Mai M, Takahashi Y, Minamoto T.
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Journal Title
Dis Colon Rectum 50(8)
Pages: 1169-81
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Peer Reviewed
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[Presentation] Distinct pathologic property of glycogen synthase kinase 3β (GSK3β) in gastrointestinal, pancreatic and liver cancers.胃がん, 大腸がん, 膵がんと肝がんに共通するglycogen synthase kinase 3β(GSK3β)の病的作用2008
Author(s)
Mai W, Miyashita K, Shakoori A, Shimasaki T, Yasumoto K, Yoshiharu Motoo, Kawakami K, Minamoto T.
Organizer
第67回日本癌学会学術総会
Place of Presentation
名古屋
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[Presentation] 消化器がんの新しい治療標的GSK3βの発現, 活性, 機能解析2007
Author(s)
川上和之, 麦威, 島崎猛夫, 宮下勝吉, 安本和生, 高橋豊, 大井章史, 元雄良治, 源利成
Organizer
第18回日本消化器がん発生学会総会W2
Place of Presentation
札幌
Related Report
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[Presentation] Synergistic effect of gemcitabine and GSK3β inhibitor against human pancreas cancer : GSK3β as a new therapeutic molecular target2007
Author(s)
Shimasaki T, Ishigaki Y, Zhao X, Tomosugi N, Tanaka T, Mai W, Kawakami K, Minamoto T, Motoo Y.
Organizer
Annual Meeting of American Pancreatic Association
Place of Presentation
Chicago, Illinois, U.S.A.
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[Presentation] CRD-BP mediates stabilization of βTrCP1 and c-myc mRNA in response to β-catenin signaling2006
Author(s)
Noubissi F, Elcheva I, Bhatia N, Shakoori A, Ougolkov A, Liu J, Minamoto T, Ross J, Fuchs SY, Spiegelman VS
Organizer
In : Keystone Symposia "Wnt and β-catenin Signaling in Development and Disease"
Place of Presentation
Snowbird, UT
Related Report
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[Presentation] Mechanisms of stabilization of βTrCP1 and c-myc mRNA in response to Wnt/β-catenin signaling2006
Author(s)
Noubissi F, Elcheva I, Bhatia N, Shakoori A, Ougolkov A, Liu J, Minamoto T, Ross J, Fuchs SY, Spiegelman VS
Organizer
In : Aspen Cancer Conference
Place of Presentation
Aspen, CO
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