Qianqian Sun1, Xiaojuan Yu1, Chunwei Peng2, Ning Liu1, Wentong Chen1, Hu Xu1, Hongquan Wei1, Kun Fang3, Ziwei Dong4, Chuyu Fu3, Youzhi Xu5, Wenjie Lu6. 1. Basic Medical College, Anhui Medical University, 81 MeiShan Road, Hefei, 230032, China. 2. Basic Medical College, Anhui Medical University, 81 MeiShan Road, Hefei, 230032, China; Department of Gastrointestinal Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Road, Hefei, Anhui, 230022, China. 3. Basic Medical College, Anhui Medical University, 81 MeiShan Road, Hefei, 230032, China; The First Clinical Medicine College, Anhui Medical University, 81 MeiShan Road, Hefei, 230032, China. 4. Basic Medical College, Anhui Medical University, 81 MeiShan Road, Hefei, 230032, China; The Second Clinical Medicine College, Anhui Medical University, Hefei, 230032, China. 5. Basic Medical College, Anhui Medical University, 81 MeiShan Road, Hefei, 230032, China. Electronic address: xuyouzhi@ahmu.edu.cn. 6. Basic Medical College, Anhui Medical University, 81 MeiShan Road, Hefei, 230032, China. Electronic address: wenjie63136@163.com.
Abstract
PURPOSE: Aggressively growing tumors are characterized by significant variations in metabolites, including lipids, and can involve the elevated synthesis ofde novo fatty acids. METHODS: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics and lipidomics were performed to compare human gastric cancer tissues and adjacent normal tissues from clinical patients. A series of cellular and molecular biological methods were applied to validate the lipidomics results. RESULTS: Palmitic acid (PA) was found to be significantly downregulated in gastric cancer tissues, and it was found that a high concentration of PA specifically inhibited cell proliferation and impaired cell invasiveness and migrationin vitro in AGS, SGC-7901, and MGC-803 gastric cancer cell lines. Moreover, sterol regulatory element-binding protein 1 (SREBP-1c) was activated in human gastric cancer tissues, and it promoted the expression of a series of genes associated with the synthesis of fatty acids, such as SCD1 and FASN. SREBP-1c knockdown rescued the migration and invasion defects in AGS and SGC-7901 gastric cancer cells. CONCLUSION: Taken together, our findings confirmed the variation in fatty acid synthesis in gastric cancer and identified SREBP-1c as a promising target for gastric cancer treatment.
PURPOSE: Aggressively growing tumors are characterized by significant variations in metabolites, including lipids, and can involve the elevated synthesis ofde novo fatty acids. METHODS: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics and lipidomics were performed to compare humangastric cancer tissues and adjacent normal tissues from clinical patients. A series of cellular and molecular biological methods were applied to validate the lipidomics results. RESULTS:Palmitic acid (PA) was found to be significantly downregulated in gastric cancer tissues, and it was found that a high concentration of PA specifically inhibited cell proliferation and impaired cell invasiveness and migrationin vitro in AGS, SGC-7901, and MGC-803 gastric cancer cell lines. Moreover, sterol regulatory element-binding protein 1 (SREBP-1c) was activated in humangastric cancer tissues, and it promoted the expression of a series of genes associated with the synthesis of fatty acids, such as SCD1 and FASN. SREBP-1c knockdown rescued the migration and invasion defects in AGS and SGC-7901gastric cancer cells. CONCLUSION: Taken together, our findings confirmed the variation in fatty acid synthesis in gastric cancer and identified SREBP-1c as a promising target for gastric cancer treatment.