College of Pharmacy, Sanquan College of Xinxiang Medical University, Xinxiang, Henan, China.
College of Basic Medical Science, Sanquan College of Xinxiang Medical University, Xinxiang, Henan, China.
Oxid Med Cell Longev. 2022 Feb 21;2022:3920664. doi: 10.1155/2022/3920664. eCollection 2022.
In metastasis of cancer cells, the epithelial-mesenchymal transition (EMT) is prerequired. Ferroptosis is an iron-mediated cellular death process, but whether it involves EMT regulation remains elusive. In addition, how stress responders (Nrf2) respond to the redox alteration and cross-talking between them needs to be determined. Our data revealed that DpdtbA (2,2'-di-pyridineketone hydrazone dithiocarbamate butyric acid ester) resisted TGF-1-induced EMT in gastric cancer lines (SGC-7901 and MGC-823) through ferritinophagy-mediated ROS production. Furthermore, the depletion of Gpx4 and xCT as well as enhanced lipid peroxidation indicated that DpdtbA acted as Erastin did in ferroptosis induction, which thus provided chance to explore the causal relationship between ferroptosis and EMT. Our data illustrated that ferritinophagy-mediated ferroptosis promoted the EMT inhibition. In addition, activated Nrf2 involved the regulation on both ferroptosis and EMT in response to the alteration in the cellular redox environment. In brief, ferritinophagy-mediated ferroptosis and activation of the Keap1/Nrf2/HO-1 pathway were conducive to the EMT inhibition.
在癌细胞的转移过程中，上皮-间充质转化（EMT）是必需的。铁死亡是一种铁介导的细胞死亡过程，但它是否涉及 EMT 的调节仍不清楚。此外，还需要确定应激反应（Nrf2）如何响应氧化还原变化以及它们之间的相互作用。我们的数据显示，DpdtbA（2,2'-二吡啶酮腙二硫代氨基甲酸丁酸酯）通过铁蛋白自噬介导的 ROS 产生抵抗 TGF-β1 诱导的胃癌细胞系（SGC-7901 和 MGC-823）中的 EMT。此外，Gpx4 和 xCT 的耗竭以及脂质过氧化增强表明，DpdtbA 作用类似于 Erastin 诱导铁死亡，这为探索铁死亡和 EMT 之间的因果关系提供了机会。我们的数据表明，铁蛋白自噬介导的铁死亡促进 EMT 抑制。此外，激活的 Nrf2 参与了细胞氧化还原环境变化引起的铁死亡和 EMT 的调节。简而言之，铁蛋白自噬介导的铁死亡和 Keap1/Nrf2/HO-1 通路的激活有助于 EMT 抑制。
