中山大学李隽等研究人员合作发现，LPCAT1介导的膜磷脂重塑促进铁死亡的逃避和肿瘤的生长。2024年4月26日，国际知名学术期刊《自然—细胞生物学》杂志在线发表了这一成果。

研究人员表示，细胞膜磷脂的动态重塑是为了防止磷脂过氧化引起的膜损伤并逃避铁死亡（一种由铁依赖的脂质过氧化驱动的非凋亡性细胞死亡形式），但人们对其背后的机制仍然知之甚少。

附：英文原文

Title: LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth

Author: Li, Ziwen, Hu, Yameng, Zheng, Haiqing, Li, Man, Liu, Yuanji, Feng, Rongni, Li, Xincheng, Zhang, Shuxia, Tang, Miaoling, Yang, Meisongzhu, Yu, Ruyuan, Xu, Yingru, Liao, Xinyi, Chen, Suwen, Qian, Wanying, Zhang, Qiliang, Tang, Daolin, Li, Bo, Song, Libing, Li, Jun

Issue&Volume: 2024-04-26

Abstract: The mechanisms underlying the dynamic remodelling of cellular membrane phospholipids to prevent phospholipid peroxidation-induced membrane damage and evade ferroptosis, a non-apoptotic form of cell death driven by iron-dependent lipid peroxidation, remain poorly understood. Here we show that lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a critical role in ferroptosis resistance by increasing membrane phospholipid saturation via the Lands cycle, thereby reducing membrane levels of polyunsaturated fatty acids, protecting cells from phospholipid peroxidation-induced membrane damage and inhibiting ferroptosis. Furthermore, the enhanced in vivo tumour-forming capability of tumour cells is closely associated with the upregulation of LPCAT1 and emergence of a ferroptosis-resistant state. Combining LPCAT1 inhibition with a ferroptosis inducer synergistically triggers ferroptosis and suppresses tumour growth. Therefore, our results unveil a plausible role for LPCAT1 in evading ferroptosis and suggest it as a promising target for clinical intervention in human cancer.

DOI: 10.1038/s41556-024-01405-y

Source: https://www.nature.com/articles/s41556-024-01405-y