...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>EBioMedicine >A Small Molecule Inhibitor of the β-Catenin-TCF4 Interaction Suppresses Colorectal Cancer Growth In Vitro and In Vivo
【24h】

A Small Molecule Inhibitor of the β-Catenin-TCF4 Interaction Suppresses Colorectal Cancer Growth In Vitro and In Vivo

机译：β-Catenin-TCF4相互作用的小分子抑制剂抑制大肠癌的体内和体外生长。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Colorectal cancer is associated with aberrant activation of the Wnt pathway. β-Catenin plays essential roles in the Wnt pathway by interacting with T-cell factor 4 (TCF4) to transcribe oncogenes. We synthesized a small molecule, referred to as HI-B1, and evaluated signaling changes and biological consequences induced by the compound. HI-B1 inhibited β-catenin/TCF4 luciferase activity and preferentially caused apoptosis of cancer cells in which the survival is dependent on β-catenin. The formation of the β-catenin/TCF4 complex was disrupted by HI-B1 due to the direct interaction of HI-B1 with β-catenin. Colon cancer patient-derived xenograft (PDX) studies showed that a tumor with higher levels of β-catenin expression was more sensitive to HI-B1 treatment, compared to a tumor with lower expression levels of β-catenin. The different sensitivities of PDX tumors to HI-B1 were dependent on the β-catenin expression level and potentially could be further exploited for biomarker development and therapeutic applications against colon cancer.
机译：大肠癌与Wnt途径的异常激活有关。 β-连环蛋白通过与T细胞因子4（TCF4）相互作用转录癌基因而在Wnt途径中起重要作用。我们合成了一个小分子，称为HI-B1，并评估了该化合物诱导的信号变化和生物学后果。 HI-B1抑制β-catenin/ TCF4荧光素酶活性，并优先引起癌细胞的凋亡，其中存活取决于β-catenin。由于HI-B1与β-catenin的直接相互作用，HI-B1破坏了β-catenin/ TCF4复合物的形成。结肠癌患者源性异种移植（PDX）研究表明，与β-catenin表达水平较低的肿瘤相比，β-catenin表达水平较高的肿瘤对HI-B1治疗更敏感。 PDX肿瘤对HI-B1的不同敏感性取决于β-catenin的表达水平，并有可能被进一步用于生物标志物的开发和对结肠癌的治疗应用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号