| 罗鸣宇,周 烨,梁 倩,邹菁华,沈 瑛.磷酸丝氨酸氨基转移酶1介导肺腺癌细胞粘附及其机制探究[J].,2021,(19):3601-3606 |
| 磷酸丝氨酸氨基转移酶1介导肺腺癌细胞粘附及其机制探究 |
| Effect and Mechanism of Cell Adhesion in Lung Adenocarcinoma Mediated by Phosphoserine Aminotransferase 1 |
| 投稿时间：2021-03-23 修订日期：2021-04-18 |
| DOI：10.13241/j.cnki.pmb.2021.19.001 |
| 中文关键词: 磷酸丝氨酸氨基转移酶 间皮素 细胞粘附 肺腺癌 |
| 英文关键词: Phosphoserine aminotransferase 1 Mesothelin Cell adhension Lung adenocarcinoma |
| 基金项目:国家自然科学基金项目（81773748；82073868）；上海市科委"科技创新行动计划"生物医药科技支撑专项项目（20S11900100） |
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| 中文摘要: |
| 摘要 目的：探究丝氨酸生物合成途径（SSP）关键酶磷酸丝氨酸氨基转移酶1（PSAT1）与肺腺癌细胞粘附的关系，并初步探讨其作用机制。方法：使用siRNA抑制PSAT1蛋白表达，观察肺腺癌细胞形态以及粘附变化，同时过表达PSAT1，反向观察PSAT1对肺腺癌细胞粘附的影响。初步探究其作用机制，采用免疫共沉淀-蛋白质谱法寻找与PSAT1直接相互作用的蛋白，筛选差异蛋白，并在过表达细胞体系中验证。结合临床公共数据库分析互作蛋白与患者预后关系。结果：发现敲低PSAT1引起肺腺癌细胞形态改变；敲低PSAT1抑制肺腺癌PC9、HCC827细胞粘附；过表达PSAT1增强PC9及HCC827细胞粘附；免疫共沉淀-蛋白质谱检测到2560个可能与PSAT1结合的蛋白，进一步通过免疫共沉淀-免疫印迹法验证PSAT1过表达使细胞中与间皮素（MSLN）结合显著上升；通过临床样本数据观察PSAT1与MSLN共同高表达的肺腺癌患者，其预后更差。结论：本文首次报道PSAT1可能通过与MSLN等蛋白-蛋白相互作用影响肺腺癌细胞粘附的新机制，提示PSAT1有望成为潜在抗肿瘤靶点，靶向其相互作用蛋白能为小分子抑制剂设计及患者个体化治疗提供新思路。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the relationship between phosphoserine aminotransferase 1 (PSAT1), a key enzyme of serine biosynthesis pathway (SSP), and the adhesion of lung adenocarcinoma cells, and to clarify the potential mechanism. Methods: Knocking down PSAT1 by siRNA to observe the morphology and adhesion changes of lung adenocarcinoma cells. Meanwhile, overexpressing PSAT1 to observe the effect of PSAT1 on the adhesion of lung adenocarcinoma cells. Immunoprecipitation-proteomic analysis was used to explore the protein that directly interacts with PSAT1, the differential proteins were screened and verified in overexpressed cells to investigate the mechanism. And the relationship between interaction proteins and patient prognosis was analyzed by clinical public database. Results: Morphological changes of lung adenocarcinoma cells was induced by knocking down PSAT1. Knockdown of PSAT1 inhibited adhesion of PC9 and HCC827 cells. Overexpression of PSAT1 enhanced the adhesion of PC9 and HCC827 cells. About 2560 proteins that may bind to PSAT1 were detected by proteomic analysis. It was further verified by co-immunoprecipitation-Western blotting the overexpression of PSAT1 promoted a significant increase in the binding of mesothelin (MSLN) in lung adenocarcinoma cells. High expression of PSAT1 and MSLN was correlated negatively with the prognosis of patients with lung adenocarcinoma according to the clinical data. Conclusion: The new mechanism was first reported that PSAT1 might affect the adhesion of lung adenocarcinoma cells by binding to MSLN and other proteins. Targeting the interacting proteins of PSAT1, a potential anti-tumor target, could provide new insights for the design of small molecular inhibitors and individualized therapy for patients. |
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