通过调节HDAC6,NF-kB促进了侵袭性细胞的形成,反过来又维持了维门丁
Jo-Mei Maureen Chen1,2, Cheng-Yen Chuang3,4, Chiao-Yun Cheng1
1Department of Applied Chemistry, National Chi Nan University, Nantou, Taiwan.
American journal of physiology. Cell physiology
|October 7, 2024
概括
核因子-kappa B (NF-κB) 通过提高HDAC6的调节来控制攻击性形成,该HDAC6维护维门丁. 抑制NF-κB增强了蛋白酶体抑制剂对癌细胞的疗效.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子生物学分子生物学
背景情况:
- 蛋白质酶抑制剂通过积累错误折叠的蛋白质,用于癌症治疗.
- 侵蚀体,维丁子封闭结构,绑定错误折叠的蛋白质,可能降低药物细胞毒性.
- 了解攻击性组合对于提高蛋白酶体抑制剂的有效性至关重要.
研究的目的:
- 描述侵略性组装的细胞机制.
- 为了研究NF-κB和HDAC6在侵略性形成中的作用.
- 探索结合NF-κB抑制与蛋白酶体抑制剂的治疗策略.
主要方法:
- 用蛋白酶抑制剂MG132.2.对A549细胞进行了治疗.
- 分析了侵略体形成,NF-κB转位和HDAC6表达.
- 使用化学激活剂/抑制剂和淘汰技术操纵NF-κB和HDAC6.
主要成果:
- 在A549细胞中,MG132治疗诱导了侵略体的形成和NF-κB核转位.
- NF-κB激活上调调了HDAC6,该HDAC6与Vimentin相互作用,以维持攻击性子.
- 抑制NF-κB与MG132协同作用,增加癌细胞死亡率.
结论:
- 通过对HDAC6进行上调,NF-κB决定了攻击性组装,HDAC6稳定了维门丁.
- 通过NF-κB/HDAC6途径形成的侵略性细胞可以保护癌细胞免受蛋白酶体抑制剂的影响.
- NF-κB抑制剂代表了一种潜在的策略,以加强癌症的蛋白酶体抑制剂疗法.
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