乙酸通过ACSS2-介导的乙-CoA生产驱动卵巢癌静止状态
Allison C Sharrow1, Emily Megill2, Amanda J Chen3
1Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Magee-Womens Research Institute, Pittsburgh, PA, USA.
代谢酶ACSS2通过重编程新陈代谢来驱动卵巢癌细胞的静止. 这种与抗性相关的代谢转变表明,静止影响了癌症治疗的有效性.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 细胞周期调节细胞周期调节
背景情况:
- 静止,一个可逆的细胞周期退出,传统上被视为一种代谢不活跃的状态.
- 最近的研究表明,代谢重编程伴随着肌肉细胞的静止.
- 代谢变化在驱动癌细胞静止中的作用尚不清楚.
研究的目的:
- 为了调查代谢重编程是否驱动卵巢癌的静止.
- 为了确定参与癌细胞静止的关键代谢酶.
主要方法:
- 多omics方法包括RNA-Seq.
- 在卵巢癌细胞中分析ACSS2表达和活性.
- 患者数据分析,将ACSS2表达与临床结果相关联.
主要成果:
- 在静止的卵巢癌细胞中,ACSS2 (乙-CoA合成酶2) 被上调,对它们的生存至关重要.
- 增加的ACSS2活性导致乙酸衍生乙-CoA的升高.
- 通过ACSS2诱导或酸盐补充,可以触发可逆静止.
- 在炎瘤细胞中,ACSS2被上调,并与抗性和较差的结果相关.
结论:
- 在卵巢癌中,ACSS2介导的代谢重编程驱动了静止.
- 代谢驱动的静止可能会影响对基化疗的治疗反应.
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