超代谢状态与小鼠和人类癌细胞中昼夜节律扰乱有关
Daniel Maxim Iascone1, Xue Zhang2,3,4, Patricia Bafford2,3
1Howard Hughes Medical Institute, Chronobiology and Sleep Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
bioRxiv : the preprint server for biology
|November 28, 2023
概括
细胞代谢显著影响昼夜节律,特别是在癌症中. 高糖解或氧化酸化会破坏这些节奏,而较低的新陈代谢会加强它们,提供新的治疗点.
科学领域:
- 生物化学 生物化学
- 时间生物学 时间生物学
- 癌症生物学 癌症生物学
背景情况:
- 细胞代谢和昼夜节律之间的交叉对多细胞生命至关重要.
- 这种沟通的中断与癌症等退行性疾病有关.
研究的目的:
- 研究昼夜节律对癌症特定代谢途径的依赖.
- 确定代谢异质性如何影响瘤细胞中的昼夜功能.
主要方法:
- 鼠标胰腺腺癌细胞克隆的代谢概况.
- 从已识别的克隆中生成昼夜记者线.
- 用代谢调节剂 (贝萨纤维酸,罗诺) 治疗.
- 对来自人类患者的黑色素瘤细胞系的分析.
主要成果:
- 代谢表型与瘤细胞中昼夜节律强度相关.
- 低代谢克隆显示出更强的节奏;高代谢克隆显示出更弱的节奏.
- 贝扎菲布拉特 (PPAR激动剂) 在一些线路上降低了昼夜振幅.
- 轮在低代谢 (低糖解) 瘤细胞中增强了节律.
- 人类黑色素瘤细胞显示了代谢活动和昼夜强度之间的负相关性.
结论:
- 癌症中的代谢异质性直接影响昼夜功能.
- 升高的糖解或氧化酸化独立地破坏了癌细胞的昼夜节律.
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