Cancer Early Detection and Prevention Initiative, Vanderbilt Ingram Cancer Center, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Department of Nutrition, Byrdine F. Lewis School of Nursing and Health Professions, Georgia State University, Atlanta, 30302, USA.
Oncogene. 2018 Sep;37(36):5007-5019. doi: 10.1038/s41388-018-0307-z. Epub 2018 May 23.
Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival. Our results demonstrated that 1) xCT was highly expressed at the cytoplasmic membrane in non-small cell lung cancer (NSCLC), 2) the expression of xCT was correlated with advanced stage and predicted a worse 5-year survival, 3) targeting xCT transport activity in xCT overexpressing NSCLC cells with sulfasalazine decreased cell proliferation and invasion in vitro and in vivo and 4) increased dependence on glutamine was observed in xCT overexpressed normal airway epithelial cells. These results suggested that xCT regulate metabolic requirements during lung cancer progression and be a potential therapeutic target in NSCLC.
许多肿瘤增加了对葡萄糖、胱氨酸或谷氨酰胺的摄取和依赖。这些关于癌细胞代谢的基本观察结果为癌症研究开辟了多个新的诊断和治疗途径。最近的研究表明，吸烟可以诱导口腔癌细胞中 xCT（SLC7A11）的表达，这表明 xCT 的过表达可能支持肺癌的进展。我们假设 xCT 在肺癌细胞中的过表达是为了满足生长和存活的代谢需求。我们的研究结果表明：1）xCT 在非小细胞肺癌（NSCLC）的细胞质膜中高度表达；2）xCT 的表达与晚期阶段相关，并预测 5 年生存率较差；3）用柳氮磺胺吡啶靶向 xCT 过表达 NSCLC 细胞中的 xCT 转运活性，可降低体外和体内的细胞增殖和侵袭；4）在 xCT 过表达的正常气道上皮细胞中观察到对谷氨酰胺的依赖性增加。这些结果表明，xCT 调节肺癌进展过程中的代谢需求，可能成为 NSCLC 的潜在治疗靶点。
