表皮-介质细胞过渡激活YAP,驱动恶性进展和免疫逃避
Xi Huang1, Mingyan Zhang1,2, Alexander D Pearce3
1Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Cancers
|September 13, 2025
概括
表皮-介质细胞过渡 (EMT) 通过抑制WWC1激活YAP信号,促进癌症转移和免疫逃避. 向YAP可能会克服EMT驱动的癌症的治疗阻力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症信号传递 癌症信号传递
背景情况:
- 表皮-介质细胞过渡 (EMT) 驱动癌症转移和治疗耐药性.
- 不完全理解EMT诱导恶性表型的分子机制.
- 同时针对不同的EMT表型仍然是一个挑战.
研究的目的:
- 研究EMT与癌细胞恶性性质之间的分子联系.
- 确定关键的信号通路,调解与EMT相关的表型.
- 探索针对EMT驱动的癌症的治疗策略.
主要方法:
- 研究了由EMT诱导的ZEB转录因子对WWC1的调节.
- 评估了Hippo信号通路活动和YAP转录程序.
- 利用药理学YAP抑制来评估其在EMT表型中的作用.
- 分析了YAP诱导的免疫检查点蛋白的表达 (VSIR,PD-L2).
主要成果:
- EMT转录因子直接抑制了WWC1,损害了Hippo的信号传输,并激活了YAP.
- 激活的YAP促进了与EMT相关的细胞迁移,入侵,生存和生长.
- 抑制YAP抑制了这些EMT驱动的恶性表型.
- YAP激活诱导免疫检查点蛋白VSIR和PD-L2,赋予对T细胞的抵抗力.
结论:
- 在癌症中,EMT通过WWC1抑制,一种非遗传机制内在激活YAP.
- 激活的YAP是EMT相关的恶性瘤和免疫逃避的关键调解者.
- 药理学YAP向可以抑制EMT表型并增强抗PD-1免疫疗法的疗效.
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