准ABCA12受控的胺稳态抑制了乳腺癌干细胞功能和化学抵抗
Jihong Cui1,2, John R Christin1,2, Julie A Reisz3
1Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Science advances
|December 1, 2023
概括
癌症干细胞 (CSCs) 依赖于脂质代谢. 向胺水平可以通过调节YAP-SOX9通路来抑制CSC并克服化学抵抗.
科学领域:
- 在瘤学瘤学.
- 癌症生物学 癌症生物学
- 脂质代谢 脂质代谢是什么
背景情况:
- 癌症干细胞 (CSCs) 是瘤进展,转移和治疗耐药性的关键驱动因素.
- 在CSC中脂质代谢的具体作用和调节尚未得到充分理解.
- CSCs在其生存和功能方面对脂质代谢具有独特的依赖性.
研究的目的:
- 研究脂质代谢在癌症干细胞功能和化学抵抗中的作用.
- 为了确定抑制CSC和克服化学抵抗的新型治疗点.
- 阐明CSC中特定脂质调节的信号通路.
主要方法:
- 从乳腺瘤模型中对CSC隔离开发基于SOX9的记者.
- 对高SOX9的CSC进行了转录和脂质组分析.
- 功能性研究涉及ABCA12下调和胺水平操纵.
- 在患者衍生的异种移植中评估CSC丰富和化学抵抗.
主要成果:
- 高SOX9的CSC可以调节脂质载体ABCA12.
- 低调ABCA12降低了CSC的干度和化学抵抗.
- ABCA12通过降低细胞内胺水平来维持细胞内胺.
- 胺通过YAP-SOX9信号通路抑制CSC干.
- 高胺增加了化疗敏感性,并减少了CSC丰富.
- 高SOX9和高ABCA12的细胞有助于人类异种移植中的化学抵抗.
结论:
- 已经确定了一种新的CSC抑制脂质代谢途径,涉及ABCA12和胺.
- 针对这种途径,特别是通过增加胺水平,可以抑制CSCs.
- 这种方法有可能在各种癌症中克服化学抵抗.
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