在癌细胞中氧化应激下,内质网膜压力和溶酶体功能障碍之间的联系
Mariapia Vietri1, Maria Rosaria Miranda1, Giuseppina Amodio2
1Department of Pharmacy, University of Salerno, Via G. Paolo II, 84084 Fisciano, SA, Italy.
Biomolecules
|July 29, 2025
概括
氧化应激驱动癌症的进展,通过恶化 lysosomal 和内分泌网膜 (ER) 功能障碍. 针对这些相互关联的压力路径提供了一个有希望的癌症治疗策略.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 溶解体和内等质网膜 (ER) 应激对于癌细胞的生存和适应至关重要.
- 氧化应激 (OS) 是一个关键的瘤微环境因素,加剧了 lysosomal 和 ER 功能障碍.
- 癌细胞利用ER应激反应,如展开的蛋白质反应 (UPR),以提高OS耐受性和促进生存.
研究的目的:
- 探索溶酶体功能障碍,ER压力和癌症中的OS相互关联的作用.
- 为了阐明驱动这些细胞过程之间的交叉通话的机制.
- 突出瘤进展和治疗耐药性的影响.
主要方法:
- 审查现有的关于溶酶体功能障碍,ER压力,氧化压力和癌症的文献.
- 对涉及的分子通路的分析,包括UPR信号 (PERK,IRE1,ATF6).
- 检查反应性氧物种 (ROS) 在破坏ER蛋白折叠和 lysosomal 功能中的作用.
主要成果:
- 癌细胞中ROS的升高会破坏ER蛋白折叠,并损害 lysosomes,导致功能障碍.
- 持久性OS激活了UPR,并促进了溶酶体膜通透性 (LMP),影响了细胞命运 (生存或死亡).
- 由于 lysosomal 功能障碍而导致的自功能障碍会放大氧化损伤,创造一个恶性循环,促进瘤的进展和治疗抵抗.
结论:
- ROS诱导的ER压力和溶酶体功能障碍之间的交叉是癌症进展,代谢适应和治疗耐药性的关键驱动因素.
- 通过增加OS和促进细胞亡,向溶酶体和ER应激反应,为癌症治疗提供了一个可行的治疗策略.
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