Shear stress enhances anoikis resistance of cancer cells through ROS and NO suppressed degeneration of Caveolin-1
Shear stress enhances anoikis resistance of cancer cells through ROS and NO suppressed degeneration of Caveolin-1
复制标题
剪切应力通过ROS和NO抑制Caveolin-1的变性增强癌细胞的失巢抵抗力
DOI：
10.1016/j.freeradbiomed.2022.10.271
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发表时间：
2022
影响因子：
7.4
通讯作者：
Yiyao Liu
中科院分区：
文献类型：
--
作者：
Xiangyan Chen;Qiong Xia;Ningwei Sun;Hailei Zhou;Zhihao Xu;Xi Yang;Ran Yan;Ping Li;Tingting Li;Xiang Qin;Hong Yang;Chunhui Wu;Fengming You;Xiaoling Liao;Shun Li;Yiyao Liu
循环肿瘤细胞（CTC）在循环系统中经历流动剪切应力后获得增强的抗失巢凋亡能力。我们前期的研究表明低切应力（LSS）通过Cav-1依赖的内源性和外源性凋亡途径促进人乳腺癌细胞抗失巢凋亡。然而，LSS如何增强悬浮癌细胞中Cav-1表达的潜在机制仍不清楚。在此，我们发现LSS诱导的氧化还原信号参与调节悬浮培养的癌细胞中Cav-1水平和抗失巢凋亡。LSS（2dyn/cm ~ 2）可明显诱导人乳腺癌MDA-MB-231细胞产生ROS和·NO，从而促进细胞活力，减少癌细胞凋亡。清除ROS和·NO可通过干扰泛素化抑制Cav-1的上调，从而抑制悬浮肿瘤细胞的抗失巢凋亡能力。这些发现为LSS刺激的ROS和·NO产生通过抑制泛素化和蛋白酶体降解增加悬浮癌细胞中Cav-1稳定性的机制提供了新的见解，这可能是转移性肿瘤治疗的潜在靶点。
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 cellsviacaveolin‐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.