Yanmei Peng, Xuetao Lei, Qingbin Yang, Guofan Zhang, Sixiao He, Minghao Wang, Ruoyu Ling, Boyang Zheng, Jiayong He, Xinhua Chen, Fengping Li, Qiming Zhou, Liying Zhao, Gengtai Ye, Guoxin Li
Helicobacter pylori, particularly cytotoxin-associated gene A (CagA)-positive strains, plays a key role in the progression of gastric cancer (GC). Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in malignant and infectious diseases, but the role of CagA in ferroptosis in cancer cells has not been determined. Here, we report that CagA confers GC cells sensitivity to ferroptosis both in vitro and in vivo. Mechanistically, CagA promotes the synthesis of polyunsaturated ether phospholipids (PUFA-ePLs), which is mediated by increased expression of alkylglycerone phosphate synthase (AGPS) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), leading to susceptibility to ferroptosis...
February 21, 2024: Experimental & Molecular Medicine