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Updated: Jul 5, 2025

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Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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PRMT5协调EGFR和AKT网络,以激活NFκB并促进EMT
bioRxiv : the preprint server for biology
|January 23, 2024
概括
蛋白质氨酸甲基转移酶5 (PRMT5) 通过调节表皮-介质细胞转变 (EMT) 来驱动高风险神经母细胞瘤转移. 抑制PRMT5抑制了瘤生长和EMT,提供了一个潜在的治疗策略.
科学领域:
- 儿科瘤学 儿科瘤学
- 癌症转移 癌症转移
- 分子生物学分子生物学
背景情况:
- 高风险神经母细胞瘤在儿科癌症中构成了重大挑战,尽管目前的治疗方法,死亡率很高.
- 表皮-介质细胞过渡 (EMT) 是瘤细胞扩散和转移的一个关键过程,与患者的不良结果有关.
- 之前的研究发现PRMT5通过AKT甲基化作为EMT的调节者,促进转移.
研究的目的:
- 调查PRMT5在调节高风险神经母细胞瘤上皮层-介质细胞过渡 (EMT) 程序中的作用.
- 阐明PRMT5控制EMT的分子机制,重点关注其与EGFR和AKT通路的相互作用.
- 在神经母细胞瘤的临床前模型中评估PRMT5抑制的治疗潜力.
主要方法:
- 研究了PRMT5.5对表皮生长因子受体 (EGFR) 的直接转录调节.
- 分析了PRMT5,EGFR和AKT信号通路之间的相互作用,用于编排NFκB激活和EMT转录因子表达.
- 利用向PRMT5甲基转移酶活性的小分子抑制剂来评估对信号通路,EMT标记物和瘤生长in vivo的影响.
主要成果:
- 发现PRMT5直接调节EGFR转录,独立调节EGFR和AKT通路.
- PRMT5调节NFκB的激活,导致对EMT转录因子ZEB1,SNAIL和TWIST1.1的上调调节.
- EGFR和AKT形成一个补偿反循环,加强EMT转录因子表达;PRMT5抑制破坏了这一循环,并消除了瘤生长in vivo.
结论:
- 在高风险神经母细胞瘤中,PRMT5在控制EMT程序方面发挥着关键作用.
- 向PRMT5甲基转移酶活性会破坏EGFR/AKT信号轴并抑制EMT.
- 抑制PRMT5有效地消除了瘤生长in vivo,突出了其治疗潜力.
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