COMPASS复合体保持了通过UPS中细胞子群传递的转移能力
Ga I Ban1, Vijitha Puviindran1, Yu Xiang2
1Department of Orthopedic Surgery, Duke University School of Medicine, Durham, NC, USA.
iScience
|July 11, 2024
概括
研究人员发现,Setd1a调节了肉瘤细胞的转移潜力. 抑制COMPASS复合物抑制了小鼠模型中的转移,揭示了癌症传播的关键表观遗传驱动因素.
科学领域:
- 在瘤学瘤学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症生物学 癌症生物学
背景情况:
- 内异质性是癌症的标志,包括未分化形肉瘤 (UPS).
- 一个特定的细胞子集,转移性克隆 (MC),驱动UPS中的转移.
- 了解转移潜力的调节者对于开发向疗法至关重要.
研究的目的:
- 为了确定关键的调节者维持转移性表型在UPS转移性克隆.
- 阐明导致肉瘤转移的表观遗传机制.
- 评估针对特定监管者的治疗策略.
主要方法:
- 利用基于CRISPR的基因组查in vivo来识别转移调节者.
- 进行了转录组和染色体测序,以分析基因表达和表观遗传修饰.
- 研究了Setd1a及其向基因Cxcl10在转移中的作用.
- 在小鼠UPS和人类异种移植模型中测试了COMPASS复合抑制剂.
主要成果:
- 确定了Setd1a,一个COMPASS复合体成员,对于维持小鼠UPS中MC的转移性表型至关重要.
- Setd1a 枯竭显著抑制了MC中转移的发展.
- 发现Cxcl10,一个COMPASS点基因,在MC细胞下调;其在非MC细胞中的删除增强了转移潜力.
- 在UPS异种移植中,COMPASS复杂抑制抑制了转移,但没有影响原发性瘤生长.
结论:
- 由COMPASS复合体驱动的表观遗传程序,特别是Setd1a,保持了肉瘤亚群的转移潜力.
- Cxcl10在调节转移性细胞行为的过程中发挥作用.
- 向COMPASS复合体是一种有前途的治疗策略,可以抑制肉瘤转移.
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