Activation of SREBP-1c alters lipogenesis and promotes tumor growth and metastasis in gastric cancer

作者：Sun, Qianqian; Yu, Xiaojuan; Peng, Chunwei; Liu, Ning; Chen, Wentong; Xu, Hu; Wei, Hongquan; Fang, Kun; Dong, Ziwei; Fu, Chuyu; Xu, Youzhi^*; Lu, Wenjie^*

来源：Biomedicine & Pharmacotherapy, 2020, 128: 110274.

DOI：10.1016/j.biopha.2020.110274

• Lipidomics
• Gastric cancer
• SREBP-1c
• Palmitic acid
• Cancer therapy

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 elementbinding 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.

• 出版日期2020-8
• 单位安徽医科大学