Analysis of the molecular mechanisms by which CDX2 supresses colon caner cell proliferation

CDX2抑制结肠癌细胞增殖的分子机制分析

• 批准号: 22790380
• 负责人: AOKI Koji
• 金额: $ 2.5万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22790380/
• 关键词: CDX2; 細胞増殖; 大腸癌; 癌抑制遺伝子; 転写; 細胞生存

CDX2 is a homebox transcription factor that is expressed specifically in the intestinal epithelial cells. We have previously shown that CDX2 supresses colonic tumorigensis, using a knockout mouse model. In this study, we have found that CDX2 suppresses proliferation of colon cancer cells through its non-transcriptional function, wheares it acts as a transcription factor. The block of cell proliferation caused by CDX2 is mediated partilly through increased level of p27 protein, a CDK inhibitor. In addition, we have found ubiqutin E1-like enzyme ATG7 as a protein interacting with CDX2, and that CDX2 stimulates autophagy. Interestingly, CDX2 induces a kind of cell death through autophagy. Thease results have suggested that CDX2 suppresses colonic tumorigensis through ATG7-mediated stimulation of autophagy.

CDX2是一种同源盒转录因子，在肠上皮细胞中特异性表达。我们先前已经使用基因敲除小鼠模型表明CDX2抑制结肠肿瘤发生。在这项研究中，我们发现CDX 2通过其非转录功能抑制结肠癌细胞的增殖，而它作为转录因子。CDX 2引起的细胞增殖阻滞部分通过CDK抑制剂p27蛋白水平的增加介导。此外，我们发现泛素E1样酶ATG7作为与CDX2相互作用的蛋白质，并且CDX2刺激自噬。有趣的是，CDX2通过自噬诱导一种细胞死亡。这些结果表明，CDX2通过ATG7介导的自噬刺激抑制结肠肿瘤的发生。

项目成果

Suppression of Colon Cancer Metastasis by Aes through Inhibition of Notch Signaling

• DOI: 10.1016/j.ccr.2010.11.008
• 发表时间: 2011-01-18
• 期刊: CANCER CELL
• 影响因子: 50.3
• 作者: Sonoshita, Masahiro;Aoki, Masahiro;Taketo, Makoto Mark
• 通讯作者: Taketo, Makoto Mark

CDX Transcription Factors Positively Regulate Expression of Solute Carrier Family 5, Member 8 in the Colonic Epithelium

• DOI: 10.1053/j.gastro.2009.10.047
• 发表时间: 2010-02-01
• 期刊: GASTROENTEROLOGY
• 影响因子: 29.4
• 作者: Kakizaki, Fumihiko;Aoki, Koji;Taketo, Makoto M.
• 通讯作者: Taketo, Makoto M.

Runx3 is reuired for full activation of regulatory T cells to preventcolitis-associated tumor formation

Runx3 需要完全激活调节性 T 细胞以预防结肠炎相关肿瘤的形成

• 发表时间: 2011
• 期刊: Journal of Immunology
• 影响因子: 4.4
• 作者: Aoki K;Sugai M;Osato M;Nambu Y;Ito K;Taketo MM and Shimizu A.
• 通讯作者: Taketo MM and Shimizu A.

Suppression of colonic polyposis byhomeoprotein CDX2 through its no transcriptional function that stabilizes p27Kip1

同源蛋白 CDX2 通过稳定 p27Kip1 的无转录功能抑制结肠息肉病

• 发表时间: 2011
• 期刊: Cancer Research
• 影响因子: 11.2
• 作者: Aoki K;Kakizaki F;Sakashita H;Manabe T;Aoki M;and Taketo MM
• 通讯作者: and Taketo MM

Suppression of Colonic Polyposis by Homeoprotein CDX2 through its Nontranscriptional Function that Stabilizes p27Kip1

• DOI: 10.1158/0008-5472.can-10-2842
• 发表时间: 2011-01-15
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Aoki, Koji;Kakizaki, Fumihiko;Taketo, Makoto M.
• 通讯作者: Taketo, Makoto M.