压缩诱导的NF-κB激活通过排毒化物维持了瘤细胞的生存,并促进了转移
Bing Liu1, Min Liu1, Yajuan Zhang2
1Key Laboratory of Multi-Cell Systems, Shanghai Key Laboratory of Molecular Andrology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
癌细胞使用阿尔代脱酶1家族B1成员 (ALDH1B1) 在狭窄的空间中生存,防止铁亡并帮助转移. 抑制CSK23或ALDH1B1可以阻止这一过程.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 转移是癌症死亡的主要原因.
- 在转移期间,使癌细胞在狭窄的空间中生存的代谢适应性尚未得到充分理解.
研究的目的:
- 为了确定对瘤细胞生存至关重要的代谢酶,在封闭的微环境中.
- 阐明调节转移的机械代谢途径.
主要方法:
- 一个体内CRISPR屏幕针对代谢酶.
- 研究化脱酶1家族B1成员 (ALDH1B1) 在转移中的作用.
- 分析氨酸激酶2α3 (CSK23) 介导的NF-κB通路的激活.
主要成果:
- ALDH1B1对于毛细血管中的瘤细胞生存至关重要.
- 压力激活CSK23,导致NF-κB通路激活和ALDH1B1上调.
- 通过ALDH1B1介导的化物解毒抑制了铁亡,促进了转移.
- 抑制CSK23或ALDH1B1可以减少转移.
- 肺癌患者中ALDH1B1和NF-κB激活的升高与转移性复发相关.
结论:
- 一个涉及CSK23,NF-κB和ALDH1B1的新型机械代谢途径促进了转移.
- 通过抑制ferroptosis,ALDH1B1的上调促进了癌细胞在狭窄的空间中的生存.
- CSK23和ALDH1B1是抑制转移的潜在治疗点.
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