Abnormal Differentiation in Cancer Cells and Intracellular Signaling

癌细胞的异常分化和细胞内信号传导

• 批准号: 17014066
• 负责人: KIKUCHI Akira
• 金额: $ 91.33万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17014066/
• 关键词: がん; Wnt; シグナル伝達; 分化; 極性; 接着; 転移; がん遺伝子; がん抑制遺伝子; Wnt5a; 胃癌; 細胞接着斑; インテグリン; 細胞周期; ラミニン5γ2; 細胞運動; JunD; 前立腺癌; Wnt-5a; 翻訳後修飾; 胃がん; β-カテニン; PKA; SUMO; PIASy; GSK-3; h-prune

In this study we focused in Wnt signaling among many intracellular signaling pathways involved in tumorigenesis. We analyzed the molecular mechanisms of tumorigenesis by abnormality in Wnt signaling in the light of differentiation and polarity. The following points are clarified. (1) Wnt proteins were purified and the roles of their post-translational modifications were clarified. (2) Receptor-mediated endocytic routes played a role in the selective activation of multiple Wnt signaling. (3) Wnt5a signaling regulated cell migration and cell polarity. (4) Abnormalities in Wnt5a signaling were involved in aggressiveness of human cancer. (5) Novel binding proteins to GSK-3, a protein kinase, were identified, and they were involved in the regulation of microtubule dynamics and focal adhesion. (6) Dvl regulated spindle dynamics and spindle assemble dynamics in mitosis.

在这项研究中，我们重点关注参与肿瘤发生的许多细胞内信号通路中的 Wnt 信号通路。我们从分化和极性的角度分析了 Wnt 信号异常导致肿瘤发生的分子机制。澄清以下几点。 (1)纯化Wnt蛋白并阐明其翻译后修饰的作用。 (2)受体介导的内吞途径在多种Wnt信号的选择性激活中发挥作用。 (3)Wnt5a信号调节细胞迁移和细胞极性。 (4) Wnt5a信号传导异常与人类癌症的侵袭性有关。 (5)鉴定出与GSK-3（一种蛋白激酶）的新型结合蛋白，它们参与微管动力学和粘着斑的调节。 (6)Dvl调节有丝分裂中的纺锤体动力学和纺锤体组装动力学。

项目成果

Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signaling.

Wnt-5a 的翻译后棕榈酰化和糖基化对其信号传导是必需的。

• 发表时间: 2007
• 期刊: Biochem. J. 402
• 作者: Kurayoshi;M.;et. al.
• 通讯作者: et. al.

Regulation of cell adhesion and migration by Wnt5a signaling

Wnt5a 信号传导调节细胞粘附和迁移

• 发表时间: 2009
• 作者: Kikuchi;A.
• 通讯作者: A.

Wntシグナルによるがんの悪性化

Wnt信号导致癌症恶性转化

• 发表时间: 2007
• 作者: Kikuchi;A.;菊池章
• 通讯作者: 菊池章

Wnt5aはlaminin-5γ2の発現を介して胃癌細胞の転移能を促進する

Wnt5a通过层粘连蛋白-5γ2的表达促进胃癌细胞的转移潜能

• 发表时间: 2008
• 作者: Kikuchi;A.;菊池章;菊池章;松本真司;菊池章;菊池章;山本英樹;山本英喜
• 通讯作者: 山本英喜

GSK-3・ regulates proper mitotic spindle formation in cooperation with a component of the がγ-tubulin ring complex, GCP5.

GSK-3 与 γ-微管蛋白环复合物 GCP5 的组成部分合作调节适当的有丝分裂纺锤体形成。

• 发表时间: 2008
• 期刊: J.Biol.Chem. 283
• 作者: Izumi,N.;Fumoto,K.;Izumi,S.;Kikuchi,A
• 通讯作者: Kikuchi,A