脂多糖酸刺激A549细胞迁移通过p-Tyr 42 RhoA和脂酶D1活动
Shohel Mahmud1,2, Amir Hamza1, Yoon-Beom Lee1
1Department of Biochemistry, College of Medicine, Hallym University, Hallymdaehag-Gil 1, Chuncheon 24252, Kangwon-do, Republic of Korea.
Biomolecules
|January 26, 2024
概括
炎症诱导的超氧化物产生激活了p-Tyr42 RhoA和脂酶D1 (PLD1) 来产生酸 (PA). 然后,与PA结合的Myosin IIA (MYH9) 调节ZEB1的表达,促进癌细胞迁移.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 细胞迁移是转移和癌症死亡率的关键驱动因素.
- 表皮-介质细胞过渡 (EMT) 启动转移,涉及改变的EMT标记蛋白表达.
- 炎症与癌症的发展和转移有关.
研究的目的:
- 阐明关联炎症,细胞迁移和EMT的分子机制.
- 确定参与脂聚糖 (LPS) 诱导的细胞迁移和EMT的关键蛋白质.
主要方法:
- 研究了通过RhoA,ROCK2和p47phox.通过LPS诱导的超氧化物生成.
- 分析了p-Tyr42 RhoA,PLD1和酸 (PA) 在超氧化物生产和EMT中的作用.
- 鉴定并描述了Myosin IIA (MYH9) 作为一种PA结合蛋白.
- 利用共免疫沉来研究蛋白质复合体的形成.
- 检查了细胞质和细胞核中的蛋白质定位.
- 评估了蛋白质与ZEB1促进体的关联.
- 采用siRNA敲击来抑制基因表达.
主要成果:
- 通过p-Tyr42 RhoA,ROCK2和p47phox,LPS触发了超氧化物生成.
- p-Tyr42 RhoA激活PLD1,通过PLD1和PA促进超氧化物产生.
- PA调节EMT蛋白表达,MYH9被确定为一种PA结合蛋白.
- MYH9促进细胞迁移和EMT标记物的改变.
- 一个由p-Tyr42 RhoA,PLD1和MYH9组成的复合体形成并定位到细胞质和细胞核.
- 这些蛋白质与ZEB1促进体结合,它们的淘汰抑制了ZEB1mRNA水平.
结论:
- p-Tyr42 RhoA和PLD1产生PA,该PA与MYH9.9结合.
- 这个复合体调节ZEB1的表达,促进癌细胞迁移.
- 这些发现揭示了一种新的炎症途径,驱动转移.
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