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

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 center dot NO generation, which promoted the cell viability and reduced the cancer cell apoptosis. Furthermore, ROS and center dot 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 center dot 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.

Automated summary

The study found that circulating tumor cells acquire enhanced anti-anoikis abilities after experiencing flow shear stress in the circulatory system, with redox signaling involved in the regulation of Cav-1 level and anoikis resistance in suspended cancer cells.