Jalmukhambetova Aiman, Baltabekova Aidana, Tolebay Aizhan, Rakhimgerey Nargiz, Molnár Ferdinand, Thanh Pham Tri, Burska Agata N, Sarbassov Dos D
Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, Kazakhstan.
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan.
Cell Stress. 2025 Aug 7;9:182-193. doi: 10.15698/cst2025.08.310. eCollection 2025.
An imbalanced production of reactive oxygen species (ROS) is linked to various aspects of cancer development, including cytoskeletal remodelling. However, the relationship between ROS, actin and cellular stiffness remains controversial. Here, we show that oxidative stress increases cortical stiffness in pre-apoptotic colon and pancreatic cancer cells via localized F-actin polymerization in the apical cortex - independent of changes in total F-actin levels. Using atomic force microscopy and flow cytometry, we demonstrate this effect across multiple ROS inducers: the combination of arsenic trioxide and -enantiomer of vitamin C, hydrogen peroxide, and rotenone. These findings explain previously debated relationships on how ROS influence actin organization, which may affect cellular stiffness. By separating total from cortical actin effects, our study reveals a redox-sensitive mechanism that governs cytoskeletal remodelling and may impair cancer cell migration.
活性氧（ROS）生成失衡与癌症发展的各个方面相关，包括细胞骨架重塑。然而，ROS、肌动蛋白和细胞硬度之间的关系仍存在争议。在此，我们表明氧化应激通过顶端皮质中局部F-肌动蛋白聚合增加凋亡前结肠癌细胞和胰腺癌细胞的皮质硬度，而与总F-肌动蛋白水平的变化无关。使用原子力显微镜和流式细胞术，我们在多种ROS诱导剂中证实了这种效应：三氧化二砷与维生素C的对映体、过氧化氢和鱼藤酮的组合。这些发现解释了先前关于ROS如何影响肌动蛋白组织的争议关系，这可能会影响细胞硬度。通过区分总肌动蛋白和皮质肌动蛋白的作用，我们的研究揭示了一种氧化还原敏感机制，该机制控制细胞骨架重塑并可能损害癌细胞迁移。
