通过尼沙林S-氨基基化来调节细胞迁移的降氧调节
Madhu C Shivamadhu1, Dhanushika S K Kukulage1, Rayavarapu Padmavathi1
1Department of Chemistry, Drexel University, Philadelphia, PA, 19104, USA.
Free radical biology & medicine
|November 10, 2025
概括
尼沙林 (NISCH) 是一种瘤抑制剂,被活性氧物种 (ROS) 改变,以调节细胞迁移. 针对这种修改提供了潜在的乳腺癌治疗方法.
科学领域:
- 降解毒素生物学和癌症研究,专注于细胞信号传递和转移.
背景情况:
- 反应性氧物种 (ROS) 在氧化还原信号传递和影响细胞迁移,入侵和癌症进展方面至关重要.
- 控制细胞迁移和入侵的特定氧化还原作用者仍然在很大程度上未被确定.
- 尼沙林 (NISCH) 是一种已知的瘤抑制剂,涉及到细胞过程.
研究的目的:
- 识别参与细胞迁移和入侵的新型氧化还原作用者.
- 阐明尼沙林 (NISCH) 影响细胞运动的机制.
- 探索向尼沙林 (NISCH) 在乳腺癌中的治疗潜力.
主要方法:
- 在Cys185中使用野生型和C185S突变乳腺癌细胞系 (MCF7,MDA-MB-231) 进行了尼沙林 (NISCH) S-谷氨基化研究.
- 在氧化应激条件下评估细胞迁移,入侵和蛋白质-蛋白质相互作用 (NISCH与Rac1,PAK1,整合蛋白α5).
- 开发并测试了工程NISCH PX-LRR结构,以抑制癌细胞表型的能力.
主要成果:
- 尼沙林 (NISCH) 在Cys185处经历S-氨基化,这种修饰降低了其与Rac1和PAK1.1的结合.
- 这种解离激活了Rac1和PAK1,促进了actin动态,增强了细胞迁移和入侵,特别是在氧化应激下.
- 设计的NISCH PX-LRR结构,特别是C185S突变,有效地抑制了乳腺癌细胞的迁移,入侵和殖民地形成.
结论:
- 确定尼沙林 (NISCH) 作为细胞迁移和侵入的新型氧化还原敏感调节剂.
- 证明在Cys185的Nischarin (NISCH) 的S-glutathionylation通过调节Rac1/PAK1信号来促进乳腺癌细胞的运动.
- 尼沙林 (NISCH) 衍生疗法显示,通过抑制转移,有望治疗乳腺癌.
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