线粒体基因组转移驱动了邻近的结肠上皮细胞中的代谢重编程,促进了TGFβ1介导的瘤进展
Bingjie Guan1, Youdong Liu1, Bowen Xie1
1Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Nature communications
|April 30, 2024
概括
来自结肠癌 (CC) 细胞的细胞外囊泡 (EV) 中的线粒体DNA (mtDNA) 通过改变邻近细胞的新陈代谢来促进瘤的进展. 这种EV-mtDNA转移可能成为CC的新生物标志物和治疗标.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 非瘤成分显著影响结肠癌 (CC) 的进展.
- 结直肠细胞和相邻的结直肠上皮细胞 (CECs) 之间的细胞间通信至关重要,但尚未完全理解.
研究的目的:
- 为了研究细胞外囊泡介导的线粒体DNA (mtDNA) 转移在结肠癌进展中的作用.
- 阐明由瘤细胞衍生的mtDNA影响邻近的CECs的机制.
主要方法:
- 对结肠癌患者的完整线粒体基因组 (mtDNA) 血清细胞外囊泡 (EV) 的分析.
- 研究携带mtDNA (EV-mtDNA) 的瘤细胞衍生的EVs对CEC的影响.
- 评估线粒体呼吸,反应性氧物种 (ROS) 生产和CEC中的TGFβ1表达.
主要成果:
- 完整的mtDNA在CC患者的血清EV中富含,与瘤阶段相关.
- 在CEC中,EV-mtDNA转移增强了线粒体呼吸和ROS生产.
- EV-mtDNA在CEC上调节TGFβ1表达,通过TGFβ/Smad通路促进瘤的进展.
结论:
- 通过EVs进行细胞间mtDNA转移是驱动大肠癌中膜代谢交叉的关键机制.
- EV-mtDNA充当结肠癌进展的重要促进者.
- EV-mtDNA具有作为结肠癌生物标志物和治疗点的潜力.
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