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Updated: Jan 24, 2026

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Induction and Analysis of Epithelial to Mesenchymal Transition
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通过对抗R循环并使转录重编程成为可能,ATR保护了表皮细胞到半机细胞的过渡
Parasvi S Patel1, Jacob P Matson1, Xiaojuan Ran2
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, United States of America.
The Journal of clinical investigation
|January 22, 2026
概括
准癌细胞的可塑性至关重要. 研究表明,ATR激酶抑制会破坏像EMT这样的细胞状态过渡,通过破坏癌细胞的稳定性来减少瘤生长和转移.
科学领域:
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
- 基因组不稳定性 基因组不稳定性
背景情况:
- 癌细胞的可塑性,由转录重编程驱动,促进转移和治疗抵抗.
- 细胞状态转变,如上皮细胞转移到介质细胞转变 (EMT),对于瘤进展至关重要.
- 这些转变的治疗向在很大程度上仍未被探索.
研究的目的:
- 调查细胞状态转换是否可以在治疗上被准.
- 阐明ATR激酶在EMT期间调节转录重编程中的作用.
- 为了确定ATR抑制作为癌症治疗的潜力.
主要方法:
- 作为一个模型系统,利用了上皮细胞到介质细胞的过渡 (EMT).
- 研究了ATR抑制对EMT期间基因组不稳定性的影响.
- 分析了R循环形成,转录复制冲突和SNAI1位点的基因调节.
主要成果:
- 在细胞状态转换期间的转录重编程会通过R循环和转录复制冲突诱导基因组的不稳定.
- ATR激酶对于细胞状态转换至关重要,保护基因组完整性并使转录重编程成为可能.
- 在EMT期间ATR抑制增加了基因组不稳定性,破坏了转录重编程,并在SNAI1.1上提高了R循环相关的DNA损伤.
- 抑制ATR会触发SNAI1和其他EMT基因的抑制,减少瘤生长和体内转移.
结论:
- 通过保持基因组完整性和促进转录重编程,ATR激酶保护细胞状态转换.
- 抑制ATR是一种有前途的治疗策略,可以向癌症的可塑性并抑制瘤的进展.
- 向ATR可以消除接受EMT的癌细胞,提供一种对抗转移和治疗耐药性的新方法.
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