在结直肠癌细胞中,TRAP1通过PGC-1α/TFAM信号通路调节线粒体生物发生
Giuseppina Bruno1, Michele Pietrafesa2, Fabiana Crispo2
1Medical Oncology and Biomolecular Therapy Unit, Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71122, Foggia, Italy. giuseppina.bruno@unifg.it.
Journal of molecular medicine (Berlin, Germany)
|August 29, 2024
概括
分子伴侣TRAP1在结直肠癌 (CRC) 中过度表达. TRAP1沉默促进了线粒体生物发生,这表明它在CRC代谢适应中的作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症新陈代谢 癌症新陈代谢
背景情况:
- 代谢重新连接对于癌细胞的适应和生存至关重要.
- 线粒体功能,包括线粒体生物发生 (MB) 和线粒体细胞吸收,是代谢适应的核心.
- TRAP1,一个分子伴侣,在结肠直肠癌 (CRC) 中表达过度,并与预后不佳和各种癌细胞功能有关.
研究的目的:
- 研究TRAP1在调节结直肠癌中的线粒体动态中的作用.
- 探索TRAP1表达与CRC中的线粒体生物发生之间的关系.
主要方法:
- 分析TRAP1表达及其与线粒体编码的呼吸链蛋白在CRC细胞系和人类CRC细胞系的转录和转化水平的相关性.
- 在TRAP1沉默后评估线粒体质量,线粒体DNA复制号 (mtDNA-CN) 和MB.
- 调查PGC-1α/TFAM信号通路对TRAP1调制的反应.
主要成果:
- 在CRC中观察到TRAP1和线粒体编码的呼吸链蛋白之间存在逆相关性.
- 沉默TRAP1导致线粒体质量增加和mtDNA-CN.
- 通过PGC-1α/TFAM通路,TRAP1沉默增强了线粒体生物发生,促进了新的功能线粒体和代谢转向氧化酸化.
结论:
- 在人类CRC细胞中,TRAP1参与调节线粒体生物发生.
- 在CRC中,TRAP1表达与线粒体基因表达和功能相反相关.
- 向TRAP1可能是调节癌细胞代谢和CRC中的线粒体功能的治疗策略.
关键词:
结肠直肠癌是一种癌症.代谢过程中的代谢.线粒体生物发生是线粒体生物发生.过氧体扩散激活受体玛协激活剂α1-ααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααααTNF受体关联蛋白1 是一种TNF受体关联蛋白.转录因子是线粒体A的转录因子.
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