The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer.

The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer.
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DOI:
10.3389/fonc.2022.858462
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发表时间:
2022
影响因子:
4.7
通讯作者:
DelGiorno KE
DelGiorno KE
中科院分区:
医学3区
文献类型:
--
作者:
Jyotsana N;Ta KT;DelGiorno KE

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SLC7A11/XCT是一种反向转运蛋白,介导胞外半胱氨酸的摄取以换取谷氨酸。半胱氨酸被还原为半胱氨酸,半胱氨酸是谷胱甘肽合成的限速前体;这一过程保护细胞免受氧化应激,因此对细胞生长、增殖和新陈代谢至关重要。SLC7A11在不同的组织中表达,通过调节氧化还原动态平衡、代谢灵活性/营养依赖性、免疫系统功能和铁下垂等过程,在包括癌症在内的各种疾病的病理生理过程中发挥不同的功能。SLC7A11的表达与肿瘤的不良预后和耐药有关,因此是一个重要的治疗靶点。在这篇综述中,我们讨论了SLC7A11在正常组织和疾病组织中的分子功能,特别是它如何调节胃肠道肿瘤。此外,我们总结了目前针对SLC7A11的治疗策略以及治疗的新途径。
SLC7A11/xCT is an antiporter that mediates the uptake of extracellular cystine in exchange for glutamate. Cystine is reduced to cysteine, which is a rate-limiting precursor in glutathione synthesis; a process that protects cells from oxidative stress and is, therefore, critical to cell growth, proliferation, and metabolism. SLC7A11 is expressed in different tissues and plays diverse functional roles in the pathophysiology of various diseases, including cancer, by regulating the processes of redox homeostasis, metabolic flexibility/nutrient dependency, immune system function, and ferroptosis. SLC7A11 expression is associated with poor prognosis and drug resistance in cancer and, therefore, represents an important therapeutic target. In this review, we discuss the molecular functions of SLC7A11 in normal versus diseased tissues, with a special focus on how it regulates gastrointestinal cancers. Further, we summarize current therapeutic strategies targeting SLC7A11 as well as novel avenues for treatment.
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