Role and Mechanism of Lipid Metabolism-mediated Ferroptosis in the Progression of Tumors
10.13865/j.cnki.cjbmb.2024.11.1298
- VernacularTitle:脂质代谢介导的铁死亡在肿瘤进展中的作用及机制
- Author:
Liao ZHANG
1
;
Zai LUO
1
;
Chen HUANG
1
Author Information
1. 上海交通大学医学院附属第一人民医院胃肠外科,上海 200080
- Publication Type:Journal Article
- Keywords:
ferroptosis;
lipid metabolism;
gastric cancer(GC);
colorectal cancer(CRC)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(3):353-363
- CountryChina
- Language:Chinese
-
Abstract:
Ferroptosis is a new form of programmed cell death with iron-dependent lipid peroxidation as its core.A variety of metabolites are involved in the regulation of ferroptosis,among which lipid metabo-lism plays an important role.The most classic lipid metabolism-mediated ferroptosis mechanism is that phospholipids containing polyunsaturated fatty acyl chain(PUFA-PLs)located on biological membranes undergo super-threshold peroxidation,which leads to the destruction of membrane structure and function.In addition,special lipids containing polyunsaturated fatty acid(PUFA),such as phospholipid with dia-cyl-PUFA tails(PL-PUFA2),polyunsaturated ether phospholipid(PUFA-ePL),cholesterol ester con-taining polyunsaturated fatty acyl chain(PUFA-CE)have also been found to be involved in the ferropto-sis process by providing PUFA for peroxidation.Lipid droplets was also found to regulate the sensitivity of ferroptosis through storing and releasing PUFA.Intermediates and derivatives of cholesterol metabolism are mainly involved in the negative regulation of ferroptosis,whereas different classes of sphingolipids were reported to have inconsistent regulatory directions for ferroptosis.A large number of previous studies have confirmed that ferroptosis is closely related to the metastasis and drug resistance of gastrointestinal tumors,therefore,we further summarized the lipid metabolism mechanisms related to ferroptosis resist-ance in gastrointestinal tumor cells,such as weakening the anabolism and peroxidation processes of PU-FA-PLs,enhancing the ferroptosis defense system and so on.At the same time,we elaborated on the re-lationship between cholesterol metabolism,lipid drop metabolism,sphingolipid metabolism,and ferropto-sis resistance in gastrointestinal tumors.Targeting these specific lipids,metabolic enzymes,and pathways to regulate ferroptosis has important clinical potential value.It is expected to provide new ideas for finding new diagnostic and prognostic markers,therapeutic drugs,and reversing chemotherapy resistance for gas-trointestinal tumors.
