肺癌在全球的发病率和死亡率均居首位。肺癌细胞生长需要两大因素：对营养物质的需求和抵抗活性氧（ROS）造成的损伤。研究表明还原型谷胱甘肽（GSH）在清除ROS中具有重要作用，但其在肺癌中产生的调控机制研究较少。我们前期研究发现谷氨酸转运体SLC1A1在肺癌中表达增加，促进GSH合成，在肺癌抗ROS中具有重要作用；结合小鼠早期炎症易感表型，进一步分析发现炎症信号分子NF-κB参与SLC1A1的转录调控。由此我们假设：炎症信号分子NF-κB转录调控SLC1A1表达，促进GSH合成，参与肺癌抗氧化应激。本课题拟通过稳定同位素碳13标记的代谢流追踪实验，阐明SLC1A1通过上调胱氨酸摄取和谷氨酸转运促进GSH合成；并进一步证实NF-κB参与SLC1A1转录调控。本项目通过对SLC1A1在肺癌发生发展中生物学功能和作用机制的研究，将炎症与代谢联系起来，为肺癌的靶向治疗联合抗炎治疗提供新思路。

Lung cancer ranks first in morbidity and mortality worldwide. Cancer cells have to generate large amount of glutathione (GSH), the major antioxidant within cells, to buffer oxidative stress. Although recent researches had reported the important role of GSH in anti-ROS, the regulatory mechanism in lung cancer was unclear. Our previous data showed the reprogramming of GSH metabolism in lung tumorigenesis via upregulated glutamate transporter SLC1A1. Moreover, two putative sites for NF-κB-mediated transcriptional activation were identified in the promoter of SLC1A1. So, we hypothesized that NF-κB induced the expression of glutamate transporter SLC1A1, which involved in anti-oxidative stress in lung cancer through generating GSH. We intend to use the isotope 13C metabolic flow tracking experiment to clarify that SLC1A1 promotes GSH synthesis by promoting cystine uptake. Besides, luciferase reporter system and chromatin immunoprecipitation assay will clarify that NF-κB is involved in the transcriptional regulation of SLC1A1. This subject will link the inflammation and lung cancer metabolism through the study of the biological function and mechanism of SLC1A1 in lung tumorigenesis, which will provide new strategies of targeting therapy combined with anti-inflammation therapy for lung cancer.