System Xc^(-)在肿瘤中的调控研究进展

Research progress on the system Xc^(-) regulation in tumor

铁死亡是一种新的调节性细胞死亡形式,这个过程由铁依赖的活性氧(reactive oxygen species,ROS)积累引起。细胞内的ROS主要受还原型谷胱甘肽(reduced glutathione,GSH)调控。GSH是细胞内主要的抗氧化剂,是由system Xc^(-)从细胞外摄入胱氨酸,再经过一系列反应合成的。System Xc^(-)是细胞膜上的一种胱氨酸/谷氨酸逆向转运蛋白,在调控细胞铁死亡过程中发挥关键作用。已有的研究证实,system Xc^(-)在多种类型的肿瘤中呈异常高表达,并与肿瘤的生长、侵袭、转移和耐药性等方面密切相关。本文将介绍system Xc^(-)在铁死亡中的作用,重点阐述system Xc^(-)在肿瘤细胞中的表达以及形成调控机制,以期为肿瘤治疗提供新的思路。

Ferroptosis is a new form of regulatory cell death, which is induced by iron-dependent accumulation of reactive oxygen species(ROS). Intracellular ROS is mainly regulated by reduced glutathione(GSH). GSH is the predominant antioxidant inside the cell, it’s synthesis is mediated by the extracellular cystine, which is uptaken into cells by system Xc. Then the cystine converts into cysteine, and generates GSH through a series of reactions. System Xcis a cystine/glutamate antiporter on the cell membrane, which plays a critical role in regulating ferroptosis. Many studies have confirmed that system Xcis abnormally highly expressed in a variety of cancers, which is closely related to growth, invasion, metastasis and drug resistance of tumor cells. This review will introduce the role of system Xcin ferroptosis, focusing on the regulation mechanism of expression and formation of system Xcin tumor cells in order to provide new ideas for cancer treatment.