针对BACH1和线粒体代谢的有效结合疗法
Jiyoung Lee1, Ali E Yesilkanal1, Joseph P Wynne1
1Ben May Department for Cancer Research, University of Chicago, Chicago, IL, USA.
Nature
|March 8, 2019
概括
在癌细胞中准BTB和CNC同质1 (BACH1) 重新编程线粒体代谢. 这使得瘤对甲胺等抑制剂更加敏感,
科学领域:
- 癌症学
- 癌症新陈代谢
- 分子生物学
背景情况:
- 线粒体代谢是癌症治疗的关键目标.
- 三重阴性乳腺癌 (TNBC) 的治疗选择有限.
- 重新编程代谢途径可以提高代谢抑制剂的疗效.
研究的目的:
- 研究BTB和CNC同质性1 (BACH1) 在癌症中的线粒体代谢中的作用.
- 确定向BACH1是否可以使癌细胞对线粒体抑制剂敏感.
主要方法:
- 研究了BACH1对葡萄糖利用和电子运输链 (ETC) 基因表达的影响.
- 使用shRNA和血红蛋白诱导的降解减少了BACH1.
- 使用抗血的BACH1突变来拯救表型.
- 评估细胞系和患者衍生的瘤生长.
- 人类瘤中相关的BACH1和ETC基因表达.
主要成果:
- 在三碳酸循环中,BACH1的表达减少了葡萄糖的利用.
- BACH1对ETC基因的转录进行负面调节.
- 减少BACH1会使癌细胞对甲胺等ETC抑制剂产生敏感性.
- 在临床前模型中,针对BACH1抑制了瘤生长.
- 在乳腺癌和其他瘤中,BACH1表达与ETC基因表达相反相关.
结论:
- 在癌症中,BACH1在调节线粒体代谢方面起着至关重要的作用.
- 向BACH1可以使乳腺癌和其他瘤对线粒体抑制剂敏感.
- 这项研究强调BACH1是提高癌症治疗效率的潜在治疗点.
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