LPCAT1-mediated membrane phospholipid remodelling promotes ferroptosis evasion and tumour growth.
Nat Cell Biol
; 26(5): 811-824, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38671262
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfolipídeos
/
Ferroptose
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1-Acilglicerofosfocolina O-Aciltransferase
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2024
Tipo de documento:
Article