β-catenin驱动的癌症需要YAP1转录复合体才能存活和产生瘤
Joseph Rosenbluh1, Deepak Nijhawan, Andrew G Cox
1Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
致癌性β-catenin (β-catenin) 通过与YAP1和TBX5.5形成复合体来驱动癌症. 抑制YES1激酶会破坏这个复合体,阻止β-catenin依赖癌症的生长.
科学领域:
- 分子瘤学分子瘤学
- 癌症生物学 癌症生物学
- 信号传输 信号传输
背景情况:
- 在结肠癌和其他癌症中,Wnt/β-catenin信号传递至关重要.
- 瘤性β-catenin调节癌症发病和进展中的关键过程.
研究的目的:
- 研究β-catenin在癌症转变中的作用.
- 为了确定依赖于β-catenin活动的信号通路.
主要方法:
- 在85个癌症细胞系中基因组规模的功能丧失屏幕.
- 分析β-catenin活动及其相关的信号合作伙伴.
- 在体外和体内研究使用小分子抑制剂的yes1.
主要成果:
- β-catenin活性癌症取决于涉及YAP1.1的信号通路.
- YAP1和TBX5与β-catenin形成一个复合体.
- YES1对YAP1进行酸化,使该复合物局部化为抗瘤基因促进体 (BCL2L1,BIRC5).
- 在β-catenin依赖性癌症中,ES1抑制减少了扩散.
结论:
- 一个β-catenin-YAP1-TBX5复合体对于β-catenin驱动的癌症的转变和生存至关重要.
- 针对YES1为这些癌症提供了潜在的治疗策略.
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