通过RACGAP1/RhoA GTPase/YAP1信号传递,PLAGL2促进了膀癌的进展
Hualin Chen1, Wenjie Yang1, Yingjie Li1
1Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.
Cell death & disease
|July 15, 2023
概括
通过激活RACGAP1/RhoA GTPase/YAP1信号通路,PLAGL2促进了膀癌 (BCa) 的进展. 用simvastatin或verteporfin抑制这种途径抑制了BCa细胞的生长和转移.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 在各种癌症中,包括膀癌 (BCa),PLAGL2被上调.
- 对于PLAGL2在BCa瘤发生中的作用的确切机制尚未完全理解.
研究的目的:
- 阐明PLAGL2对膀癌的进展有所贡献的分子机制.
- 研究PLAGL2对BCa.细胞增殖和转移的影响.
主要方法:
- 在BCa组织中分析PLAGL2表达和与生存的相关性.
- 在PLAGL2缺乏后的体外和体外功能测定.
- RNA测序,qRT-PCR,免疫阻塞,免疫光,光酶记者和ChIP测试.
- 研究PLAGL2对Hippo通路,YAP1/TAZ,RACGAP1和Rhoa激活的作用.
- 使用RhoA抑制剂 (simvastatin) 和YAP1/TAZ抑制剂 (verteporfin) 的治疗.
主要成果:
- 在BCa组织中观察到PLAGL2过度表达,并与较差的生存率相关.
- 在体外和体内,PLAGL2缺乏抑制了BCa细胞的增殖和转移.
- PLAGL2破坏了Hippo路径,通过对RACGAP1进行交换激活并激活RhoA,增加了YAP1/TAZ活动.
- 在BCa中,simvastatin和verteporfin治疗取消了PLAGL2介导的增殖和增殖效应.
结论:
- 通过RACGAP1/RhoA GTPase/YAP1信号轴,PLAGL2促进了膀癌的进展.
- 针对这种信号通路中的关键节点,如RhoA或YAP1/TAZ,为BCa.提供了潜在的治疗策略.
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