葡萄糖诱导的RYBP抑制了瘤细胞的有氧糖解和迁移
Xiuyuan Chen1, Weijia Liu1, Tangai Li1
1Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
Biochemical and biophysical research communications
|May 12, 2024
概括
环1和YY1结合蛋白 (RYBP) 水平随着瘤细胞中的葡萄糖的增加而上升,抑制糖解和迁移. 这揭示了RYBP在癌症代谢和营养相互作用中的新作用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 细胞代谢 细胞代谢
背景情况:
- 环1和YY1结合蛋白 (RYBP) 已知在发育,分化,亡和瘤发生中的作用.
- RYBP的全部功能范围,特别是在癌症中营养代谢的背景下,仍然在很大程度上未被探索.
研究的目的:
- 调查RYBP在调节瘤细胞代谢中的作用,以应对不同的葡萄糖度.
- 阐明葡萄糖对RYBP调节的基础机制及其对癌细胞行为的影响.
主要方法:
- 在不同葡萄糖条件下对RYBP蛋白水平的定量分析在人类瘤原生和非瘤原生细胞系中.
- 通过抑制多基化和蛋白质体降解来研究RYBP蛋白质稳定.
- 测量细胞外酸化率 (ECAR) 和乳酸生产以评估糖解.
- 在不同的葡萄糖条件和RYBP表达水平下评估瘤细胞迁移 (Knockdown/Knockout).
主要成果:
- 在瘤细胞中,RYBP蛋白水平随着葡萄糖的增加而增加,但在非瘤细胞中降低.
- 葡萄糖通过抑制其多比基因化和蛋白质体降解来稳定瘤细胞中的RYBP.
- RYBP抑制瘤细胞糖解,在RYBP过度表达时,ECAR和乳酸盐产量下降,并在敲击时增加水平.
- RYBP对糖溶解的影响独立于葡萄糖的摄取.
- 高葡萄糖增强瘤细胞迁移,特别是在缺乏RYBP的细胞中,这表明RYBP在葡萄糖介导的迁移调节中的作用.
结论:
- RYBP在调节瘤细胞新陈代谢和迁移方面发挥着新的关键作用,以应对葡萄糖的可用性.
- 这些发现强调了RYBP作为营养素和癌细胞代谢重编程之间的相互作用的关键调解者.
- 这项研究为了解和准癌症代谢开辟了新的途径.
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