向翻译和细胞循环反向影响CTC新陈代谢但不影响转移
Tetiana Y Bowley1, Seth D Merkley1, Irina V Lagutina2
1Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
Cancers
|November 14, 2023
概括
向蛋白质转化和细胞增殖与奥马素和palbociclib减少黑色素瘤大脑转移 (MBM) 在小鼠. 这种双重方法通过向核糖生成和细胞可塑性来抑制转移有能力的循环瘤细胞 (CTC).
科学领域:
- 在瘤学瘤学.
- 癌症转移 癌症转移
- 分子生物学分子生物学
背景情况:
- 黑色素瘤脑转移 (MBM) 是预后不佳的重要原因,通常是死后诊断的.
- 循环瘤细胞 (CTC) 是转移性传播的关键驱动因素.
- 一个之前识别的CTC RPL/RPS基因特征与MBM发病有关.
研究的目的:
- 调查向核子生成是否可以预防CTC衍生的异种移植中的MBM和转移.
- 在MBM模型中评估蛋白质翻译抑制剂奥马西他辛 (omacetaxine) 与CDK4/CDK6抑制剂palbociclib (palbociclib) 或没有这种蛋白质翻译抑制剂的疗效.
- 描述循环瘤细胞的代谢可塑性.
主要方法:
- 在MBM小鼠模型中,用奥马素和/或palbociclib治疗.
- 使用尸体解剖和IVIS成像来监测转移性发育.
- 从小鼠血液中获得的CTCs的RNA测序和代谢分析 (线粒体应力测试,RT-qPCR).
主要成果:
- 药物治疗显著降低了小鼠的MBM和脑外转移.
- RNA-Seq揭示了CTCs治疗后关键RPL/RPS基因的下调.
- 奥马素和palbociclib对细胞新陈代谢表现出逆效应,突出显示了双重向的重要性.
- 这项研究提供了患者衍生的循环瘤细胞的第一个功能代谢表征.
结论:
- 细胞翻译和增殖的双重向对于抑制转移能力强的CTCs的可塑性至关重要.
- 抑制核糖生成和细胞增殖有效地减少黑色素瘤大脑转移.
- 这些发现为CTCs的代谢脆弱性和MBM的潜在治疗策略提供了洞察力.
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