ACE 损失通过调节 AKT-FOXO1 来驱动细胞癌的生长和侵入
Lei Yin1,2,3, Lixin Mao4, Rui Yin5
1Department of Urology, Shidong Hospital, Yangpu District, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, 200438, People's Republic of China.
Biologics : targets & therapy
|December 24, 2024
概括
ангиотензин转化酶 (ACE) 在清细胞细胞癌 (ccRCC) 中表达不足. 更高的ACE水平与更好的ccRCC预后相关,并通过调节AKT-FOXO1通路来抑制瘤生长和转移,这表明ACE是治疗点.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 氨酸- ангиотензин- алдостерон系统 (RAAS) 与癌症进展有关.
- 在清细胞细胞癌 (ccRCC) 中RAAS的特定作用仍未得到证实.
研究的目的:
- 在ccRCC中研究血管酶转化酶 (ACE) 的表达和功能,这是一个关键的RAAS成分.
- 阐明ACE在ccRCC进展中的潜在机制及其作为治疗点的潜力.
主要方法:
- 定量RT-PCR,西斑和免疫组织化学用于ACE表达分析.
- 细胞增殖,迁移,入侵和糖解测定 (CCK-8,Transwell,海马).
- 异种移植模型,RNA-seq,ChIP和露西法酶记者试验,以探索分子机制.
主要成果:
- 在ccRCC组织和细胞系中,ACE显著表达不足.
- 高ACE表达与有利的患者预后有关.
- 过度表达ACE抑制了ccRCC细胞生长,转移和糖解,而敲击则增强了这些过程.
- 通过AKT-FOXO1信号通路,ACE抑制了ccRCC的进展和上皮-介质细胞过渡 (EMT).
- ACE增强了everolimus的抗瘤作用,其表达受到ZBTB26.6的调节.
结论:
- 在ccRCC的进展,生长和转移中,ACE起着抑制作用.
- ACE通过促进FOXO1表达来发挥其作用,这是PI3K-AKT通路的下游目标.
- 在ccRCC治疗中,ACE是潜在的治疗点.
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