Study on the signaling patlways involvedin Nox1-mediated Ras oncogene transformation

Nox1介导的Ras癌基因转化信号通路研究

• 批准号: 18590289
• 负责人: KAMATA Tohru
• 金额: $ 2.5万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590289/
• 关键词: Nox1; Ras; reactive oxygen species; Rho; LMW-PTP; ERp72; Adhesion-Invasion?; Cancer; Nox1; レドックスシグナリング; アポプトシス; 接着; 細胞形質

The aim of our study is to elucidate the role of reactive oxygen species(ROS) generating oxidase, Nox1 h signal transduction involved in Ras oncogene transformation Our previous study revealed that Nox1 was essential for maintenance of Ras oncogene transformation phenotypes, and that upregulation of Nox1 expression was associated with some types of human cancers. This dearly indicates an important role of Nox1 in the development of cancer. Through the two-year term effort, we have made significant progress as outlined below 1), We identified a redox protein ERp72 as a potential target for Nazi. Nox1 oxidizes ERp72 and thereby regulates its nectox activity in response to activation of EGF receptor, suggesting that Nart-ERp72 complexes are coupled to EGF receptor signafing. 2), Nox1-generated oxidants mediate down-regulation of the Rho activity in Ras-transformed cells. This involves coridalive inactivation of LMW-PTP by Nox1 and subsequent activation of RhoGAR Then, the decreased Rho activity leads to disruption of both actin stress fhers and focal adhesions. The results provide a novel insight into the molecular mechanism underlying invasion and migration of transformed cells. Our discovery has significant implications in understandng the cell transformation mechanism and the biopharmacological.modulation of Nox1 may benefit prevention of tumor expansion.

我们的研究的目的是阐明产生氧化酶的活性氧（ROS）的作用，NOX1 H信号转导参与RAS癌基因转化的NOX1 H信号转导我们先前的研究表明，NOX1对于维持RAS癌基因转化表型至关重要，NOX1表达的上调与某些类型的人类Cancers相关。这非常表明NOX1在癌症发展中的重要作用。通过为期两年的任期，我​​们取得了重大进展，如下1），我们确定了氧化还原蛋白ERP72是纳粹的潜在目标。 NOX1氧化ERP72，从而对EGF受体的激活进行调节，从而调节其Nectox活性，这表明NART-ERP72复合物与EGF受体Signafing耦合。 2），NOX1生成的氧化剂介导了RAS转换细胞中RHO活性的下调。这涉及NOX1对LMW-PTP的结式失活以及随后的Rhogar激活，RHO活性的降低会导致肌动蛋白应激的FHER和局灶性粘连的破坏。结果为侵袭和转化细胞的迁移提供了一种新颖的见解。我们的发现对了解细胞转化机制和生物药理具有重要意义。NOX1的调节可能有益于预防肿瘤扩张。

项目成果

Nox1 plays a critical mediating role in oncogenic Ras-induced vascular endothelial growth factor expression

Nox1 在致癌 Ras 诱导的血管内皮生长因子表达中发挥关键介导作用

• 发表时间: 2008
• 期刊: Oncogene (in press)
• 作者: Komatsu;D.;et. al.
• 通讯作者: et. al.

メラノーマ細胞の癌化過程における活性酸素産生遺伝子Nox4の新しい役割

活性氧产生基因Nox4在黑色素瘤细胞癌变过程中的新作用

• 发表时间: 2007
• 作者: 古田秀一;et. al.
• 通讯作者: et. al.

A redox protein ERp/72 is a target for a superoxide generating oxidase Nox1 that mediates Ras transformation

氧化还原蛋白 ERp/72 是介导 Ras 转化的超氧化物生成氧化酶 Nox1 的靶标

• 发表时间: 2006
• 作者: Wei;Chang;et. al.
• 通讯作者: et. al.

A novel role of a superoxide generating Nox4 in cell cycle progression and transforming potential of melanoma cells

产生超氧化物的 Nox4 在黑色素瘤细胞的细胞周期进程和转化潜力中的新作用

• 发表时间: 2007
• 作者: Furuta;S.;et. al.
• 通讯作者: et. al.

メラノーマ細胞の癌化過程における活性酸素産生遺伝子Nox4の新しい役割.

活性氧产生基因Nox4在黑色素瘤细胞癌变过程中的新作用。

• 发表时间: 2007
• 作者: 古田秀一;et. al.
• 通讯作者: et. al.