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线粒体代谢驱动低密度脂蛋白诱导的乳腺癌细胞迁移
Sandrina Nóbrega-Pereira1,2, Francisco Santos2, Miguel Oliveira Santos1
1Instituto de Medicina Molecular João Lobo Antunes, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Cancer research communications
|June 28, 2023
概括
低密度脂蛋白 (LDL) 通过增强线粒体脂肪酸使用,促进三阴性乳腺癌 (TNBC) 转移. 阻断CD36或活性氧物种 (ROS) 阻断LDL驱动的TNBC细胞迁移和代谢适应.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 癌细胞生物学 癌细胞生物学
背景情况:
- 转移是癌症死亡的主要原因.
- 富含脂质的环境,包括高低密度脂蛋白 (LDL) 胆固醇,促进乳腺癌转移.
- 线粒体代谢在脂肪丰富环境中的三阴性乳腺癌 (TNBC) 转移中的作用尚不清楚.
研究的目的:
- 研究LDL如何影响TNBC细胞迁移和入侵.
- 阐明线粒体代谢在LDL诱导的TNBC转移中的作用.
- 确定预防TNBC转移的潜在治疗点.
主要方法:
- 细胞培养和TNBC的*in vivo*模型.
- 评估细胞迁移,入侵和脂质滴滴的形成.
- 线粒体质量,网络分析和代谢概况 (转录组和能量分析).
- 抑制CD36和活性氧物种 (ROS) 途径.
主要成果:
- LDL增加了脂质滴积累,CD36表达和TNBC细胞迁移和入侵.
- LDL增强了线粒体质量和迁移细胞中的网络扩散,这取决于动蛋白重塑.
- 在LDL的影响下,TNBC细胞变得依赖脂肪酸 (FA) 氧化来进行线粒体呼吸.
- 由LDL诱导的迁移和线粒体重塑需要将FA输送到线粒体中.
- 在LDL治疗后观察到长链脂肪酸的线粒体积累和ROS产量的增加.
- 阻断CD36或ROS废除的LDL诱导的细胞迁移和代谢重编程.
结论:
- LDL通过重编程线粒体新陈代谢以利用脂肪酸来促进TNBC细胞迁移和入侵.
- CD36和ROS是LDL诱导的线粒体适应和细胞迁移的关键媒介.
- 向CD36或ROS在脂质丰富的环境中为TNBC提供了潜在的抗转移性策略.
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