慢性暴露会改变细胞外囊泡,通过持续的NUPR1表达来调解癌症的进展
Shan Liu1, Max Costa1, Angelica Ortiz1
1Department of Medicine, Division of Environmental Medicine, New York University Grossman School of Medicine, New York, NY 10010, United States of America.
暴露于的癌细胞释放含核蛋白1 (NUPR1) 的细胞外囊泡 (EV). 这些EVs通过诱导皮质转移到介质细胞转变 (EMT) 和受体细胞中结独立生长来促进癌症的进展.
科学领域:
- 环境毒理学环境毒理学
- 癌症生物学 癌症生物学
- 细胞和分子瘤学细胞和分子瘤学.
背景情况:
- 细胞外囊泡 (EVs) 调解细胞间通信,促进癌症的进展.
- (Ni) 暴露会诱导表观遗传变化,导致表皮细胞转化为介质细胞转化 (EMT),这是转移至关重要的过程.
- EMT的特点是分子变化,如N-cadherin和ZEB1的增加,以及功能变化,如固定独立生长.
研究的目的:
- 研究暴露细胞中的细胞外囊泡 (EVs) 在促进癌症进展中的作用.
- 为了确定来自Ni暴露细胞的EV是否可以在接受细胞中诱导EMT.
- 为了确定这些电动车内的特定货物,并阐明它们在癌症转移中的功能.
主要方法:
- BEAS-2B细胞对 (Ni) 的暴露.
- 使用纳米粒子追踪分析 (NTA) 隔离和表征细胞外囊泡 (EVs).
- 分析EV货物,包括核蛋白1 (NUPR1) 和其对受体细胞的影响.
- 在Ni转化细胞中对NUPR1进行基因沉默.
主要成果:
- 来自Ni暴露细胞的EVs在没有Ni存在的接受BEAS-2B细胞中诱导了EMT.
- 这些EV被发现包装了转录因子核蛋白1 (NUPR1).
- 在EV中,NUPR1被转移到受体细胞中,影响其核蛋白质环境,其减少减少了EMT和固独立生长.
结论:
- 这项研究表明,NUPR1是来自Ni暴露细胞的EV中包装的关键介质,驱动癌症的进展.
- 通过EV介导的NUPR1转移促进EMT和独立于 anchorage的生长,有助于癌症转移.
- 这项研究突出了一个新的癌症进展机制,涉及NUPR1和EVs在暴露的背景下.
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