SOAT1通过SYVN1/UBIAD1/MAPK/SREBP1轴调控脂代谢促进胃癌生长和转移的作用机制研究

代谢重塑是肿瘤发生发展的重要标志之一，靶向异常改变的代谢限速酶已成为治疗肿瘤的突破口。利用生物信息学系统分析，我们从111个代谢相关的限速酶中发现脂代谢酶SOAT1可能参与胃癌的发生发展。我们初步研究发现SOAT1可以通过降低细胞内胆固醇的浓度而活化胆固醇浓度感受器SREBP1，进一步研究发现SOAT1通过结合E3泛素连接酶SYVN1降解UBIAD1，从而激活MAPK通路，促进SREBP1转录，调控脂质合成，进而促进胃癌的生长和转移。本项目拟通过细胞，类器官和动物模型，结合人群样本深入探讨SOAT1通过SYVN1/UBIAD1/MAPK/SREBP1轴促进胃癌生长和转移的作用及分子机制，为胃癌的早期分子预测与临床治疗提供科学理论依据。

Metabolic remodeling is one of the important signs of tumor occurrence and development. Targeting abnormal metabolic rate limiting enzyme has become a breakthrough in the treatment of tumor. Using bioinformatics system analysis, we found that SOAT1 may be involved in the occurrence and development of gastric cancer. In our preliminary study, we found that SOAT1 could activate the cholesterol receptor SREBP1 by reducing the cholesterol concentration in gastric cancer cells. Furthermore, we found that SOAT1 could interact with E3 ligase SYVN1 to degrade UBIAD1, resulting in MAPK activation, and MAPK pathway promoted SREBP1 transcription and lipid synthesis, resulting in the growth and metastasis of gastric cancer. This project aims to explore the role and molecular mechanism of SOAT1 in promoting the malignant process of gastric cancer via cell lines, Organoid, animal models, and population samples using molecular biological technology methods, so as to provide scientific theoretical basis for early molecular prediction and clinical treatment of gastric cancer.