在食道状细胞癌中,SLC43A2和NFκB信号通路通过反循环调节 metionin/cystine 限制诱导的铁亡
Hao Peng1,2, Yuyu Yan2, Min He2
1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei Province, China.
Cell death & disease
|June 2, 2023
概括
饮食中氨酸/氨酸的限制通过激活铁亡来抑制食道状细胞癌 (ESCC) 的进展. 这通过涉及SLC43A2和NFκB通路的新反循环发生,提供新的治疗点.
科学领域:
- 在瘤学瘤学.
- 代谢途径 代谢途径
- 细胞机制 细胞机制
背景情况:
- 饮食氨酸/氨酸限制 (MCR) 在癌症中显示出治疗前景.
- 连接MCR与食道状细胞癌 (ESCC) 的机制尚不清楚.
研究的目的:
- 阐明MCR对ESCC影响的分子和细胞机制.
- 确定ESCC治疗的潜在治疗点.
主要方法:
- 使用ECA109细胞的异种移植模型.
- RNA测序和丰富分析.
- 在体内和体外测定测量GSH,GPX4,Fe2+和MDA水平.
主要成果:
- 在ESCC异种移植中,MCR显著改变了氨酸代谢.
- 瘤进展被MCR抑制,与铁和NFκB通路激活有关.
- MCR降低了GSH和GPX4,增加了Fe2+和MDA,并通过SLC43A2.2抑制了NFκB信号传输.
结论:
- 通过SLC43A2和NFκB信号之间的正反循环,MCR通过诱导铁亡来抑制ESCC的进展.
- 这项研究提供了理论基础,并确定了ESCC中基于ferroptosis的疗法的新目标.
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