细胞迁移通过尼沙林S-氨基化进行氧调节
Madhu C Shivamadhu1, Dhanushika S K Kukulage1, Rayavarapu Padmavathi1
1Department of Chemistry, Drexel University, Philadelphia, PA 19104, USA.
bioRxiv : the preprint server for biology
|October 3, 2025
概括
尼沙林 (NISCH) 被氧化应激改变,影响乳腺癌细胞迁移. 工程NISCH变种抑制癌细胞入侵和转移,提供潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 电解氧信号传输 电解氧信号传输
背景情况:
- 活性氧物种 (ROS) 调节关键的生物过程,包括细胞迁移和侵入.
- 虽然ROS在癌症进展中的作用已知,但控制细胞迁移的特定氧化还原作用者仍然不清楚.
- 尼沙林 (NISCH) 是一种已知的瘤抑制剂,正在研究其在氧化还原介导细胞入侵中的作用.
研究的目的:
- 为了确定参与细胞迁移和入侵的特定氧化还原作用者.
- 阐明尼沙林 (NISCH) 在氧化应激下影响细胞迁移和侵入的机制.
- 探索工程NISCH构造在乳腺癌中的治疗潜力.
主要方法:
- 在Cys185.5.上研究了尼沙林 (NISCH) 的S-谷氨基化.
- 在氧化应激下,比较表达野生型NISCH的乳腺癌细胞的迁移和入侵与C185S突变细胞.
- 分析了NISCH与Rac1,PAK1和整蛋白α5.5的结合.
- 评估了工程NISCH PX-LRR结构对细胞迁移,入侵和殖民地形成的影响.
主要成果:
- 尼沙林 (NISCH) 在Cys185处经历S-氨基化,影响其与Rac1和PAK1.1的相互作用.
- 氧化应激诱导的NISCH S-氨基化通过激活Rac1/PAK1信号来增强乳腺癌细胞的迁移和入侵.
- 工程NISCH结构,特别是C185S突变,有效地抑制乳腺癌细胞迁移,入侵和殖民地形成.
结论:
- 尼沙林 (NISCH) 作为一种新型的氧化还原作用者,调节细胞迁移和侵入.
- 在氧化应激下,NISCH S-Glutathionylation是驱动乳腺癌细胞转移的关键机制.
- 通过抑制转移,NISCH衍生的蛋白质疗法在治疗乳腺癌方面表现有前途.
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