Identification of Epithelial-to-Mesenchymal Transition-Associated Genes as Therapeutic Targets for Lung Cancer

鉴定上皮间质转化相关基因作为肺癌的治疗靶点

• 批准号: 20590919
• 负责人: SATO Mitsuo
• 金额: $ 2.91万
• 依托单位: National Institute for Longevity Sciences,NCGG
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590919/
• 关键词: 上皮間葉系細胞転換; 非閉塞性肺疾患; 肺癌; 非閉塞性肺疾患癌

The aim of this study is to identify epithelial-to-mesenchymal transition (EMT)-associated genes as novel therapeutic targets for lung cancer. While several EMT-inducing genes have been discovered, which of these have the dominant role in EMT of lung cancer was not clear. We found that among four EMT-inducing genes (ZEB1, TWIST, SLUG, SIP1) ZEB1 plays the dominant role in EMT of lung cancer. Furthermore, we found that ZEB1 knockdown suppresses the growth of lung cancer cells. In addition, we also showed ZEB1 knockdown suppresses the growth of malignant pleural mesothelioma cells. These results suggest that ZEB1 may be a promising therapeutic target for lung cancer and malignant pleural mesothelioma.

本研究的目的是确定上皮-间质转化（EMT）相关基因作为肺癌的新治疗靶点。虽然已经发现了几个EMT诱导基因，但哪些基因在肺癌的EMT中起主导作用尚不清楚。我们发现在4个EMT诱导基因（ZEB1、TWIST、SLUG、SIP1）中，ZEB1在肺癌的EMT中起主导作用。此外，我们发现ZEB1敲低可以抑制肺癌细胞的生长。此外，我们还发现ZEB1敲低抑制恶性胸膜间皮瘤细胞的生长。这些结果表明，ZEB1可能是肺癌和恶性胸膜间皮瘤的一个有希望的治疗靶点。

项目成果

Knockdown of oncogenic KRAS in non-small cell lung cancers suppresses tumor growth and sensitizes tumor cells to targeted therapy.

• DOI: 10.1158/1535-7163.mct-10-0750
• 发表时间: 2011-02
• 期刊: Molecular cancer therapeutics
• 影响因子: 5.7
• 作者: Sunaga N;Shames DS;Girard L;Peyton M;Larsen JE;Imai H;Soh J;Sato M;Yanagitani N;Kaira K;Xie Y;Gazdar AF;Mori M;Minna JD
• 通讯作者: Minna JD

Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS

• DOI: 10.1073/pnas.0806158105
• 发表时间: 2008-09-16
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Guha, Udayan;Chaerkady, Raghothama;Varmus, Harold E.
• 通讯作者: Varmus, Harold E.

PIK3CA mutations and copy number gains in human lung cancers.

• DOI: 10.1158/0008-5472.can-07-5084
• 发表时间: 2008-09-01
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Yamamoto H;Shigematsu H;Nomura M;Lockwood WW;Sato M;Okumura N;Soh J;Suzuki M;Wistuba II;Fong KM;Lee H;Toyooka S;Date H;Lam WL;Minna JD;Gazdar AF
• 通讯作者: Gazdar AF

Knockdown of ZEB1, a master EMT gene, suppresses anchorage-independent cell growth of lung cancer cells.

ZEB1（一种主要的 EMT 基因）的敲除可抑制肺癌细胞的贴壁依赖性细胞生长。

• 发表时间: 2010
• 作者: 佐藤光夫;ら;et al.
• 通讯作者: et al.

抗悪性腫瘍薬コンサルトブック

抗癌药物咨询书

• 发表时间: 2010
• 作者: Mimura;et al.;南博信編集
• 通讯作者: 南博信編集