线粒体综合体I促进癌转移
Divya Bezwada1, Luigi Perelli2, Nicholas P Lesner1
1Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature
|August 14, 2024
概括
癌细胞的新陈代谢发生变化,清细胞细胞癌 (ccRCC) 抑制了线粒体活动. 然而,ccRCC转移会增加新陈代谢,这表明在癌症进展过程中会发生新陈代谢.
科学领域:
- 癌症中的代谢重编程
- 细胞癌中的线粒体功能
背景情况:
- 大多数癌都表现出代谢功能障碍.
- 这种功能障碍对人类癌症进展的影响尚不清楚.
研究的目的:
- 研究癌患者的新陈代谢程序.
- 了解新陈代谢功能如何影响清细胞细胞癌 (ccRCC) 的进展和转移.
主要方法:
- 在瘤切除期间为80多名癌患者注入13C标记的营养物质.
- 在孤立的人类脏和瘤线粒体中测量呼吸.
- 在体内和体外有机型培养以评估代谢标记.
- 用小鼠进行实验,研究线粒体功能在转移中的作用.
主要成果:
- 清细胞细胞癌 (ccRCC) 显示抑制的三碳酸 (TCA) 循环标记,表明组织内在的代谢重编程.
- 在ccRCC中较低的电子运输链活动有助于改变TCA循环标记.
- 与原发性瘤相比,转移性ccRCC表现出增强的TCA循环标记.
- 在小鼠中,刺激线粒体呼吸会促进转移,而抑制电子运输链复合物I会减少转移.
结论:
- 在癌的进展过程中,代谢特性和负债会发生变化.
- 线粒体功能是ccRCC转移的限制因素,但不是主要部位的瘤生长.
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