昆明医科大学学报2026，Vol.47Issue(3)：23-33,11.DOI:10.12259/j.issn.2095-610X.S20260303
PCK2通过SLC38A2介导的谷氨酰胺摄取促进非小细胞肺癌细胞恶性表型
PCK2 Promotes Malignant Phenotypes of Non-Small Cell Lung Cancer Cells via SLC38A2-Mediated Glutamine Uptake
摘要
Abstract
To investigate the molecular mechanism by which phosphoenolpyruvate carboxykinase 2(PCK2)regulates glutamine transport under low-glucose conditions and its impact on the malignant behaviors of non-small cell lung cancer(NSCLC)cells.Methods:Stable PCK2 knockdown(KD group)and negative control(NC group)cell lines(n=3 for all experiments)were established in the human NSCLC A549 cell line..The impact of PCK2 on the transcription and protein expression of solute carrier family 38 member 2(SLC38A2)were assessed using PRM proteomics,Western blotting,and dual-luciferase reporter assays.Cell proliferation(MTT),migration(wound healing),and apoptosis(flow cytometry)were analyzed via MTT assay,scratch wound healing assay,and flow cytometry,respectively under low-glucose conditions(1000 mg/L).Functional rescue experiments were performed by establishing a Gln supplementation group(KD+Gln group)and an SLC38A2 overexpression group(KD+SLC38A2 group).Results:Upon PCK2 knockdown,SLC38A2 promoter activity decreased by approximately 60％(P＜0.000 1)and its protein expression was significantly reduced(P＜0.01).Under low-glucose conditions,cell proliferation was inhibited in the KD group.The 24-hour migration rate(≈ 20％)was significantly lower than that in the NC group(≈ 55％,P＜0.000 1),while the apoptosis rate(≈ 13％)was significantly higher(NC group≈ 4.5％,P＜0.0001).Both glutamine supplementation and SLC38A2 overexpression significantly reversed these phenomena,restoring migration rates to approximately 50％(P＜0.01 vs.KD)and reducing apoptosis to about 5.5％(P＜0.0001 vs.KD).Conclusion:Under low-glucose stress,PCK2 maintains Gln uptake by regulating SLC38A2 expression at the transcriptional level,thereby promoting the proliferation,migration,and survival of NSCLC cells.关键词
非小细胞肺癌/磷酸烯醇式丙酮酸羧激酶2/溶质载体家族38成员2/谷氨酰胺转运/低糖环境Key words
Non-small cell lung cancer/PCK2/SLC38A2/Glutamine transport/Low glucose分类
医药卫生引用本文复制引用
阮丽波,徐克旺,赵敏君,张帆,曾文珺,张海燕..PCK2通过SLC38A2介导的谷氨酰胺摄取促进非小细胞肺癌细胞恶性表型[J].昆明医科大学学报,2026,47(3):23-33,11.基金项目
云南省科技厅-昆明医科大学应用基础研究联合专项基金(202201AY070001-236) （202201AY070001-236）
云南省张存泰专家工作站(202405AF140057) （202405AF140057）
云南省第一人民医院临床医学研究中心开放项目(2023YJZX-LN16) （2023YJZX-LN16）
云南省第一人民医院临床医学研究中心开放项目(2022YJZX-LN17) （2022YJZX-LN17）
