卡塞普辛S通过KEAP1-NRF2信号通路调节肝细胞癌中铁灭的敏感性
Ru-Chen Xu1, Jia-Lei Sun1, Fu Wang1
1Department of Gastroenterology and Hepatology, China; Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, 180 Fenglin Rd., Shanghai, China.
Redox biology
|August 10, 2025
概括
素S (CTSS) 调节铁亡,这是一种细胞死亡途径,对癌症治疗至关重要. 在肝细胞癌 (HCC) 中抑制CTSS使瘤对铁亡敏感,提供了一种新的治疗策略.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
背景情况:
- 铁亡是一种依赖于铁的编程细胞死亡,涉及脂质过氧化.
- 它为各种癌症提供了一个有前途的治疗标.
- 了解铁亡调节剂是克服治疗耐药性的关键.
研究的目的:
- 为了确定铁灭的新型调节剂.
- 为了研究Cathepsin S (CTSS) 在ferroptosis中的作用.
- 探索CTSS作为肝细胞癌 (HCC) 的治疗点.
主要方法:
- 在耐铁灭的HCC细胞中研究了CTSS表达.
- 使用了shRNA和一种特定的CTSS抑制剂 (LY3000328),用于基因/蛋白质抑制.
- 研究了CTSS调制对KEAP1-NRF2通路的影响.
- 在体内进行的研究,使用正位异种移植的小鼠模型.
主要成果:
- CTSS在耐铁灭的HCC细胞中被上调.
- 抑制CTSS使HCC细胞对铁亡产生敏感.
- 通过自-溶酶体通路降解KEAP1,CTSS促进NRF2的积累.
- 与铁灭诱导剂相结合的CTSS抑制在体内减少了HCC瘤的生长.
结论:
- 在HCC中,CTSS作为一种新型调节剂,增强了hcc中的ferroptosis.
- 向CTSS可以克服HCC患者的铁灭性耐药性.
- 抑制CTSS代表了HCC治疗的潜在治疗策略.
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