The cystine/glutamate antiporter xCT (SLC7A11) is frequently overexpressed in many cancers, including glioblastoma. Cystine taken up by the cells via xCT is reduced to cysteine, which is used to synthesize glutathione for antioxidant cellular defense. However, overexpression of xCT causes cell death under glucose-limited conditions. We found that stimulation of glioblastoma cells with epidermal growth factor (EGF) induces the upregulation of xCT and promotes cell death under glucose deprivation. Treatment with the mTOR inhibitor Torin 1 suppressed the EGF-induced upregulation of xCT and cell death. EGF increased xCT mRNA levels, which was suppressed by Torin 1. The lysosome inhibitor bafilomycin A1 increased xCT protein levels in the absence of EGF or in the presence of EGF and Torin 1. Taken together, our study suggests that EGF promotes glioblastoma cell death under glucose-limited conditions via the upregulation of xCT at transcriptional and protein levels in an mTOR-dependent manner.

胱氨酸/谷氨酸逆向转运蛋白 xCT (SLC7A11) 在许多癌症中经常过度表达，包括胶质母细胞瘤。细胞通过 xCT 吸收的胱氨酸被还原为半胱氨酸，用于合成谷胱甘肽以进行抗氧化细胞防御。然而，在葡萄糖受限的条件下，xCT 的过度表达会导致细胞死亡。我们发现用表皮生长因子 (EGF) 刺激胶质母细胞瘤细胞可诱导 xCT 上调并促进葡萄糖剥夺下的细胞死亡。用 mTOR 抑制剂 Torin 1 治疗抑制了 EGF 诱导的 xCT 上调和细胞死亡。EGF 增加了 xCT mRNA 水平，这被 Torin 1 抑制。溶酶体抑制剂巴弗洛霉素 A1 在没有 EGF 或存在 EGF 和 Torin 1 的情况下增加了 xCT 蛋白水平。