Shear stress enhances anoikis resistance of cancer cells through ROS and NO suppressed degeneration of Caveolin-1.

作者：Xiangyan Chen, Q. Xia, Ningwei Sun, Hailei Zhou, Zhihao Xu, Xi Yang, Ran Yan, Ping Li, Tingting Li, Xiang Qin, Hong Yang, Chunhui Wu, Fengming You, X. Liao, Shun Li, Yiyao Liu · 发表于：Free Radical Biology & Medicine · 年份：2022 · DOI：10.1016/j.freeradbiomed.2022.10.271 · 被引用次数：18 · 研究领域：Medicine

Circulating tumor cells (CTCs) acquire enhanced anti-anoikis abilities after experiencing flow shear stress in the circulatory system. Our previous study demonstrated that low shear stress (LSS) promotes anoikis resistance of human breast carcinoma cells via caveolin-1 (Cav-1)-dependent extrinsic and intrinsic apoptotic pathways. However, the underlying mechanism how LSS enhanced Cav-1 expression in suspended cancer cells remains unclear. Herein, we found that LSS induced redox signaling was involved in the regulation of Cav-1 level and anoikis resistance in suspension cultured cancer cells. Exposure of human breast carcinoma MDA-MB-231 cells to LSS (2 dyn/cm2) markedly induced ROS and •NO generation, which promoted the cell viability and reduced the cancer cell apoptosis. Furthermore, ROS and •NO scavenging inhibited the upregulation of Cav-1 by interfering ubiquitination, and suppressed the anoikis resistance of suspended tumor cells. These findings provide new insight into the mechanism by which LSS-stimulated ROS and •NO generation increases Cav-1 stabilization in suspended cancer cells through inhibition of ubiquitination and proteasomal degradation, which could be a potential target for therapy of metastatic tumors.