针对被破坏的Hippo信号传递,以防止瘤皮细胞免疫逃避
Xiangmin Lv1, Jiyuan Liu1, Jinpeng Ruan1
1Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nature communications
|March 25, 2025
概括
在细胞中过度激活YAP1,通过促进细胞转化和骨髓衍生抑制细胞 (MDSC) 积累,驱动乳头细胞癌 (pRCC) 的发展. 准YAP1或MDSC为pRCC提供了潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 乳头性细胞癌 (pRCC) 与Hippo/YAP途径瘤抑制剂的缺失有关.
- 需要进一步阐明Hippo/YAP信号通路在pRCC发病过程中的作用.
研究的目的:
- 用转基因小鼠模型研究YAP1过活化在pRCC发育中的作用.
- 分析YAP1诱导的PRCC启动和进展期间细胞格局的变化.
主要方法:
- 开发一种上皮细胞特异性的YAP1过活化转基因小鼠模型.
- 在癌症发育过程中对细胞变化的单细胞分辨率分析.
- 骨髓衍生抑制细胞 (MDSC) 的评估和TEAD抑制剂 (MGH-CP1) 疗效的评估.
主要成果:
- 过度激活YAP1诱导管皮细胞脱差和转变,导致pRCC.
- YAP1操纵改变了多个信号通路,促进了MDSC积累,并推动了pRCC的发展.
- MDSC枯竭抑制了YAP1诱导的脏过度生长和瘤发生;MGH-CP1通过阻碍MDSC积累来抑制瘤发育.
结论:
- 破坏的Hippo/YAP信号传输是pRCC的一个重要驱动因素.
- 针对包括YAP1和MDSCs在内的Hippo通路,为PRCC预防和治疗提供了一个可行的治疗策略.
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