通过降低Akt表达的调节,Atg5淘汰会诱导替代性自
Hye-Gyo Kim1, Myeong-Han Ro1, Michael Lee1,2
1Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-Ro, Yeonsu-Gu, Incheon, 22012 Republic of Korea.
Toxicological research
|October 2, 2023
概括
自在细胞转化中起着双重作用. 这项研究揭示了与Atg5 (自相关的5) 独立的替代性自,可能会在自受损的细胞中驱动瘤发生.
科学领域:
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
- 分子生物学分子生物学
背景情况:
- 自,一种细胞降解过程,在癌症发展中表现出复杂的作用.
- 之前的研究表明,淘汰与自相关的5 (Atg5) 会促进NIH 3T3细胞的恶性转变.
- 了解细胞转化过程中自的精确机制对于癌症研究至关重要.
研究的目的:
- 调查自在NIH 3T3细胞恶性转变中的机械作用.
- 为了比较正常,转化和Atg5缺乏细胞系的自活动和依赖性.
- 在Atg5损伤的背景下阐明替代性自诱导的途径.
主要方法:
- 使用的NIH 3T3,Atg5淘汰赛 (KO) NIH 3T3和Ras-NIH 3T3细胞系.
- 通过使用mRFP-GFP-LC3记者和Cyto-ID染色来评估自活动.
- 评价了细胞对自抑制剂的敏感性 (SBI-0206965,克洛洛昆,奥巴托克拉克斯).
- 分析了细胞活力,移动性和mTOR介导的Akt酸化 (pAkt S473).
- 通过Rab9依赖研究了通过Rab9依赖的替代性自诱导.
主要成果:
- 转变的Ras-NIH 3T3细胞显示出比正常NIH 3T3细胞更高的基础自.
- 所有转变的细胞,包括Atg5KO,对自抑制剂更敏感,表明自依赖性更高.
- 失去Atg5增强了细胞活力和移动性,特别是在Ras-NIH 3T3细胞中.
- 在Ras-NIH 3T3和Atg5KO细胞中,以Rab9依赖的方式诱导了替代性自.
- 在Atg5KO细胞中,mTOR介导的pAkt S473减少,这表明mTOR独立的替代性自.
结论:
- 与正常细胞相比,转化细胞表现出增加的自活动和依赖性.
- 当Atg5-介导的自受损时,可以诱导潜在的Rab9-依赖和mTOR-独立的替代自.
- 这种替代的自途径可能会在有缺陷Atg5依赖自的细胞中促进瘤发生.
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