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赖色素依赖的营养物质清理是表皮细胞到介质细胞过渡期间应激适应的基础
Michal J Nagiec1,2, Paola M Cavaliere2,3, Friederike Dundar4,5
1Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.
bioRxiv : the preprint server for biology
|October 3, 2025
概括
癌细胞通过改变营养吸收来平衡入侵和增殖. 侵袭性乳腺癌细胞通过溶酶体和巨细胞酶体吸收氨基酸,这种转变取决于c-MYC下调.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 代谢过程中的代谢.
背景情况:
- 转移性癌细胞表现出复杂的生存策略,包括营养应激耐受性和入侵性.
- 支持入侵的机制通常与细胞增殖相冲突.
- 了解细胞过渡状态对于建模转移至关重要.
研究的目的:
- 在乳腺癌中表皮-介质细胞过渡 (EMT) 期间定义细胞过渡状态.
- 研究平衡增殖和侵入性表型的代谢适应.
- 阐明c-MYC在调节这些过渡状态中的作用.
主要方法:
- 在乳腺上皮细胞中使用ERK2和TGF-β信号诱导EMT.
- 对内分泌体系统活动和代谢适应的分析.
- 通过巨细胞结合与血膜运输对氨基酸获取的评估.
- 操纵c-MYC水平以确定其监管作用.
主要成果:
- EMT诱导了内分泌体系统的显著上调和代谢转变.
- 侵入性细胞优先通过溶酶体和巨细胞酶体清理氨基酸,即使在营养丰富的条件下.
- 巨细胞酶增强了细胞内氨基酸的储存,有助于在剥夺期间的生存.
- 降低c-MYC的调节对于这种代谢切换和从增殖到迁移的过渡至关重要.
结论:
- 细胞在EMT期间通过特定的代谢和内分泌体适应来动态平衡增殖和入侵.
- 巨细胞和 lysosomal 清除对于侵入性细胞中氨基酸的获取至关重要.
- c-MYC下调是使这些适应性变化成为可能的关键事件,影响乳腺癌转移中的细胞过渡状态.
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