دورية أكاديمية
Helicobacter pylori CagA-mediated ether lipid biosynthesis promotes ferroptosis susceptibility in gastric cancer
العنوان: | Helicobacter pylori CagA-mediated ether lipid biosynthesis promotes ferroptosis susceptibility in gastric cancer |
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المؤلفون: | 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 |
المصدر: | Experimental and Molecular Medicine, Vol 56, Iss 2, Pp 441-452 (2024) |
بيانات النشر: | Nature Publishing Group, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Medicine LCC:Biochemistry |
مصطلحات موضوعية: | Medicine, Biochemistry, QD415-436 |
الوصف: | Abstract 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. This susceptibility is mediated by activation of the MEK/ERK/SRF pathway. SRF is a crucial transcription factor that increases AGPS transcription by binding to the AGPS promoter region. Moreover, the results demonstrated that CagA-positive cells are more sensitive to apatinib than are CagA-negative cells, suggesting that detecting the H. pylori CagA status may aid patient stratification for treatment with apatinib. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 2092-6413 |
Relation: | https://doaj.org/toc/2092-6413 |
DOI: | 10.1038/s12276-024-01167-5 |
URL الوصول: | https://doaj.org/article/9772285f58854f9fb8bcdf284b2c8d5c |
رقم الأكسشن: | edsdoj.9772285f58854f9fb8bcdf284b2c8d5c |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 20926413 |
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DOI: | 10.1038/s12276-024-01167-5 |