基于胱氨酸-谷氨酸反向转运体的抗肿瘤代谢治疗新策略

The new strategies of antimetabolic therapy of cancers based on antiporter of cystine and glutamate

代谢重编程是恶性肿瘤的重要特征之一,是促使肿瘤细胞在营养匮乏的情况下存活并促进其恶性进展的重要原因。近些年研究发现,胱氨酸-谷氨酸反向转运体(system Xc^(-))不仅是诱导铁死亡的关键靶点,同时对肿瘤代谢起重要调控作用,该转运体是导致肿瘤细胞对葡萄糖高度依赖的原因之一,这提示对于高表达system Xc^(-)的肿瘤,抑制葡萄糖摄取及糖代谢是一种有效的治疗策略。本文从system Xc^(-)的表达调控、功能及其对肿瘤代谢的影响等方面进行综述,以期为抗肿瘤代谢治疗提供新思路。

Metabolism reprogram is one of the major characteristics of malignant cancer.It promotes survival of tumor cells and launches the malignant progression of cancers under the nutrition-deficient tumor milieu.Several recent studies have revealed that the antiporter of cystine and glutamine,system Xc^(-),is a key target of ferroptosis and also impairs flexibility of tumor metabolism remolding and promotes dependency on glucose.This finding indicates that interfering glucose uptake and glucose metabolism are potential methods of treating system Xc^(-)overexpression cancers.This review summarizes the expressional regulation and metabolic functions of system Xc^(-),thereby paving a new avenue for the antimetabolic therapy of cancers.