Analysis of role of mitotic regulation and its abnormalities in carcinogenesis

有丝分裂调节及其异常在癌发生中的作用分析

• 批准号: 17013070
• 负责人: SAYA Hideyuki
• 金额: $ 86.4万
• 依托单位: Keio University (2006-2009)Kumamoto University (2005)
• 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-17013070/
• 关键词: 癌; 遺伝子; 細胞・組織; 細胞分裂; 細胞骨格; チェックポイント; 細胞運動; タンパク質分解; 病理学; シグナル伝達; 蛋白質; タンパク分解; リン酸化; オーロラキナーゼ; APC; 遺伝子改変マウス; 細胞死; 細胞老化

Abnormal regulation of G2/M progression induces the drastic phenotypic changes and the genomic instability in cells. The G2/M progression is controlled by two biochemical events, protein degradation and protein phosphorylation. Therefore, regulatory factors of these two biochemical events are considered to play a critical role in development and progression of tumors. Specific aims of our project were i) to analyze molecular mechanisms regulating the transition of G2/M phase, ii) to clarify the role of abnormal regulation of the mitotic molecules and iii) to identify the targets for cancer therapies. As the results, we could elucidate the novel functions of mitotic regulating molecules including Aurora-A, WARTS, Cdh1 and Mklp2 and, furthermore, clarify the molecular mechanism of mitotic catastrophe induced by conventional chemotherapeutic agents.

G2/M进程的异常调控可引起细胞表型的剧烈变化和基因组的不稳定性。G2/M过程受蛋白降解和蛋白磷酸化两个生化事件控制。因此，这两种生化事件的调控因子被认为在肿瘤的发生发展中起着至关重要的作用。​从而阐明Aurora-A、WARTS、Cdh1、Mklp2等有丝分裂调控分子的新功能，进一步阐明常规化疗药物诱导有丝分裂突变的分子机制。

项目成果

Experimental therapies : Investigator-initiated cancer trials with INDs for approval in Japan.

实验疗法：研究人员发起的癌症试验，并在日本批准新药申请。

• 发表时间: 2010
• 期刊: Nat Rev Clin Oncol 7
• 作者: Imamura CK.;et al
• 通讯作者: et al

The APC/C activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation.

APC/C 激活剂 Cdh1 通过靶向 p190 RhoGAP 进行降解来调节 Rho GTPase。

• 发表时间: 2010
• 期刊: Mol Cell Biol
• 影响因子: 5.3
• 作者: Naoe;Kuninaka;S;et al.
• 通讯作者: et al.

Suppression of centrosome amplification after DNA damage depends on p27 accumulation

• DOI: 10.1158/0008-5472.can-05-3250
• 发表时间: 2006-04-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Sugihara, E;Kanai, M;Miwa, M
• 通讯作者: Miwa, M

TNF-α regulates TGF-β -dependent epithelial-mesenchymal transition by promoting hyaluronan-CD44-Mcesin interaction.

TNF-α 通过促进透明质酸-CD44-Mcesin 相互作用来调节 TGF-β 依赖性上皮-间质转化。

• 发表时间: 2010
• 期刊: J Biol Chem 285
• 作者: Takahashi E.;et al
• 通讯作者: et al

The tumor suppressor WARTS activates the Oim/HtrA2-dependent pathway of cell death.

肿瘤抑制因子 WARTS 激活 Oim/HtrA2 依赖性细胞死亡途径。

• 发表时间: 2005
• 期刊: Oncogene 24
• 作者: Kuninaka;S. et al.
• 通讯作者: S. et al.