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乳酸通过表观遗传调节控制癌症干和可塑性

Nguyen T B Nguyen¹, Sira Gevers¹, Rutger N U Kok¹

¹Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CG Utrecht, the Netherlands; Oncode Institute, Utrecht, the Netherlands.

Cell metabolism

|February 11, 2025

概括

乳酸盐通过抑制癌症干细胞分化和通过BRD4.4激活MYC来促进肠道瘤的生长. 向癌症代谢和BRD4可能会防止瘤复发.

科学领域:

在瘤学瘤学.
癌症生物学癌症生物学
代谢调节代谢调节代谢调节

背景情况:

瘤与癌症干细胞 (CSC) 和癌症分化细胞 (CDC) 呈现异质性.
细胞可塑性使得CDCs能够恢复到CSCs,从而导致疗法耐药性和复发.
了解CSC和CDC代谢表型对于开发有效的癌症疗法至关重要.

研究的目的:

调查代谢变化在肠道瘤有机体发育中的作用.
确定调节CSC分化和脱分化的关键分子机制.
探索针对癌症代谢的新型治疗策略,以预防瘤复发.

主要方法:

在人类瘤器官中利用了基因编码的光记者.
采用基于机器学习的细胞追踪器CellPhenTracker,同时追踪细胞类型特征,代谢变化和细胞系.
在CSC和CDC中分析了代谢表型和表观遗传修饰.

主要成果:

在CSC和CDC中确定了不同的代谢表型.
乳酸被发现可以抑制CSC分化,并诱导去分化进入繁殖的CSC状态.
乳酸在表观遗传上通过增加基因素乙化,依赖BRD4.4的过程来激活MYC.

结论:

乳酸在调节肠道瘤动态和CSC可塑性方面发挥着至关重要的作用.
针对癌症代谢,特别是乳酸生产及其通过BRD4对MYC的下游影响,是一个有希望的战略.
与代谢向结合的BRD4抑制剂可能是预防瘤复发的有效方法.

关键词:

癌症的代谢癌症的代谢细胞的可塑性细胞的可塑性细胞类型细胞类型细胞与细胞的相互作用.不同化的差异化差异化.不同质性的异质性现场成像现场成像现场成像有机生物有机物一个单细胞追踪系统.干细胞是干细胞的组成部分.

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