LPCAT1-mediated Membrane Phospholipid Remodelling Promotes Ferroptosis Evasion and Tumour Growth

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2024 Apr 26

PMID 38671262

Authors

Ziwen Li

Yameng Hu

Haiqing Zheng

Man Li

Yuanji Liu

Rongni Feng

Xincheng Li

Shuxia Zhang

Miaoling Tang

Meisongzhu Yang

Ruyuan Yu

Yingru Xu

Xinyi Liao

Suwen Chen

Wanying Qian

Qiliang Zhang

Daolin Tang

Bo Li

Libing Song

Jun Li

Affiliations

Soon will be listed here.

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.

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