SLC7A11 是谷氨酸胱氨酸逆向转运蛋白 Xc- 系统的一个单元。其作用是输入胱氨酸进行谷胱甘肽生物合成并维持细胞内的氧化还原平衡。索拉非尼抑制 SLC7A11 的转运蛋白活性。索拉非尼已被批准用于治疗多种癌症。然而，目前我们对SLC7A11和索拉非尼在鼻咽癌（NPC）中的作用机制的了解仍然有限。我们发现鼻咽癌中SLC7A11的表达上调。 SLC7A11高表达与预后不良、转移和T分期晚期相关，可作为鼻咽癌的独立预后指标。在体外，我们观察到鼻咽癌细胞依赖胱氨酸生存。靶向 SLC7A11 会导致谷胱甘肽生物合成限制、细胞内活性氧积累、脂质过氧化物、铁死亡和细胞凋亡。同时，它改变了NPC中丝裂原激活的蛋白激酶途径，包括p38激活但ERK抑制。这限制了NPC细胞的增殖。索拉非尼在体内抑制鼻咽癌细胞的增殖并诱导其死亡。总之，SLC7A11在鼻咽癌的发生和进展中发挥着重要作用，可能成为鼻咽癌治疗的新靶点。版权所有©2023。由Elsevier B.V.出版。

SLC7A11 is a unit of the glutamate cystine antiporter Xc- system. It functions to import cystine for glutathione biosynthesis and maintains the redox balance in cells. Sorafenib inhibits the transporter activity of SLC7A11. The use of sorafenib has been approved in the treatment of multiple cancers. However, at present, our understanding of the mechanism of SLC7A11 and sorafenib in nasopharyngeal carcinoma (NPC) remains limited. We found that the expression of SLC7A11 was upregulated in NPC. A high SLC7A11 expression was associated with poor prognosis, metastasis, and an advanced T stage, which can be used as an independent prognostic indicator of NPC. In vitro, we observed that NPC cells relied on cystine for survival. Targeting SLC7A11 resulted in glutathione biosynthesis limitation, intracellular reactive oxygen species accumulation, lipid peroxides, ferroptosis, and apoptosis. Meanwhile, it altered mitogen activated protein kinase pathway, including p38 activation but ERK inhibition in NPC. This limited the proliferation of NPC cells. Sorafenib inhibited the proliferation and induced the death of NPC cells in vivo. In conclusion, SLC7A11 plays an important role in the occurrence and progression of NPC and may be a novel target for NPC treatment.Copyright © 2023. Published by Elsevier B.V.