The biological roles of YAP in malignant mesothelioma proliferation and invasion

YAP在恶性间皮瘤增殖和侵袭中的生物学作用

• 批准号: 22590375
• 负责人: MURAKAMI Hideki
• 金额: $ 2.91万
• 依托单位: Aichi Medical University (2011-2012)Aichi Cancer Center Research Institute (2010)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22590375/
• 关键词: 腫瘍; 悪性中皮腫; がん遺伝子; 細胞内シグナル; 腫瘍抑制遺伝子

We recently revealed malignant mesothelioma cell lines frequently harbor mutations of the genes associated with Hippo tumor suppressor pathway. Dysregulation of Hippo pathway leads to activation of a transcriptional co-activator Yes-associated protein (YAP) and the YAP paralog transcriptional co-activator with PDZ-binding motif (TAZ). However the detailed function of YAP/TAZ on MM cell growth or motility remains unclear. To investigate the biological roles of YAP/TAZ in MM development, we generated lentivirus mediated YAP or TAZ knock-down system in MM cells, and analyzed the changes in cell growth, motility, and the gene expression patterns with oligonucleotide microarrays. SiRNA mediated reduction of YAP/TAZ in MM cell lines suppress cell proliferation and motility. We also detected the deregulation of several genes involved in cell proliferation, apoptosis, and cytoskeleton by YAP/TAZ knockdown. Our results will provide new insights into development of mesothelioma, and give some clues to developing a new molecular target therapy for mesothelioma.

我们最近发现恶性间皮瘤细胞系经常窝藏突变的基因与河马肿瘤抑制途径。Hippo通路的失调导致转录共激活因子Yes相关蛋白（雅普）和具有PDZ结合基序的雅普旁转录共激活因子（TAZ）的激活。然而，雅普/TAZ对MM细胞生长或运动性的详细功能仍不清楚。为了研究雅普/TAZ在MM发生发展中的生物学作用，我们构建了慢病毒介导的雅普或TAZ敲减系统，并利用寡核苷酸芯片分析了细胞生长、运动和基因表达模式的变化。SiRNA介导的MM细胞系中雅普/TAZ的减少抑制细胞增殖和运动性。我们还检测到通过雅普/TAZ敲低参与细胞增殖、凋亡和细胞骨架的几个基因的失调。我们的研究结果将为间皮瘤的发生发展提供新的认识，并为开发间皮瘤的分子靶向治疗提供线索。

项目成果

LATS2 Is a Tumor Suppressor Gene of Malignant Mesothelioma

• DOI: 10.1158/0008-5472.can-10-2164
• 发表时间: 2011-02-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Murakami, Hideki;Mizuno, Tetsuya;Sekido, Yoshitaka
• 通讯作者: Sekido, Yoshitaka

Expression and functional analysis of Hairy Enhancer of Split 1 (HES1) in malignant mesothelioma cell lines

Hairy Enhancer of Split 1 (HES1)在恶性间皮瘤细胞系中的表达及功能分析

• 发表时间: 2010
• 作者: Ohbayashi;T.;Imamura;T.;村上秀樹
• 通讯作者: 村上秀樹

Induction of tubulin polymerization and apoptosis in malignant mesothelioma cells by a new compound JBIR-23

• DOI: 10.1016/j.canlet.2010.10.005
• 发表时间: 2011-01-28
• 期刊: CANCER LETTERS
• 影响因子: 9.7
• 作者: Hwang, Ji-Hwan;Takagi, Motoki;Shin-ya, Kazuo
• 通讯作者: Shin-ya, Kazuo

Induction of tubulin polymerization and apoptosis in malignant mesothelioma cells by new compound JBIR-23

新化合物JBIR-23诱导恶性间皮瘤细胞微管蛋白聚合和凋亡

• 发表时间: 2011
• 期刊: Cancer letters
• 影响因子: 9.7
• 作者: Arai A;Imadome K;Wang L;Wu N;Kurosu T;Wake A;Yamamoto H;Ota Y;Harigai M;Fujiwara S;Miura O.;Hideki Murakami;Ji-Hwan Hwang
• 通讯作者: Ji-Hwan Hwang

TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth.

• DOI: 10.1084/jem.20111653
• 发表时间: 2012-03-12
• 期刊: The Journal of experimental medicine
• 作者: Fujii M;Toyoda T;Nakanishi H;Yatabe Y;Sato A;Matsudaira Y;Ito H;Murakami H;Kondo Y;Kondo E;Hida T;Tsujimura T;Osada H;Sekido Y
• 通讯作者: Sekido Y