缺乏葡萄糖的癌细胞的进化动态:从实验性数学建模的见解
Luis Almeida1, Jérôme Alexandre Denis2,3, Nathalie Ferrand2
1Sorbonne Université, CNRS, Université de Paris, Inria, Laboratoire Jacques-Louis Lions UMR 7598, Paris 75005, France.
Journal of the Royal Society, Interface
|January 10, 2024
概括
癌细胞通过增加单碳酸盐载体 (MCT1) 来适应低葡萄糖,以重复使用乳酸. 这种由乳酸信号和表观遗传变化驱动的代谢重编程,加速了癌细胞的进化和适应.
科学领域:
- 在瘤学瘤学.
- 癌症新陈代谢 癌症新陈代谢
- 进化生物学 进化生物学
背景情况:
- 葡萄糖是癌细胞的主要能量来源.
- 单碳酸盐运输体 (MCTs) 促进癌细胞中的代谢重编程.
- 在缺乏葡萄糖的环境中,MCT1使癌细胞能够利用乳酸,从而影响疾病的进展.
研究的目的:
- 研究癌细胞适应缺乏葡萄糖的进化机制.
- 探索单碳酸载体1 (MCT1) 表达在这种适应过程中的作用.
- 了解癌细胞如何重新利用乳酸作为替代能源.
主要方法:
- 使用了结合实验数据和数学建模的协同方法.
- 开发了一种使用部分整微分方程来描述基于MCT1表达的癌细胞群体动态的数学模型.
- 使用体外乳腺癌细胞数据对模型进行校准.
主要成果:
- 通过乳酸信号传递,环境诱导的MCT1表达促进了缺乏葡萄糖的癌细胞的快速适应.
- 由于表观遗传变化的MCT1表达的波动为自然选择提供了基质.
- 这些机制加快了适应癌细胞的选择性扫除,并可能充当投注对冲策略.
结论:
- 与乳酸相关的信号通路对于快速适应葡萄糖稀缺的反应至关重要.
- 在MCT1表达的表观遗传变异推动了癌症的进化适应.
- 这项研究阐明了驱动癌细胞存活和在代谢压力下进展的关键机制.
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