Lipid reprogramming induced by the NNMT-ABCA1 axis enhanced membrane fluidity to promote endometrial cancer progression.
Aging (Albany NY)
; 15(21): 11860-11874, 2023 10 25.
Article
em En
| MEDLINE
| ID: mdl-37889548
ABSTRACT
Elucidating the mechanism for the high metastasis capacity of Endometrial cancer (EC) is crucial to improve treatment outcomes of EC. We have recently reported that nicotinamide N-methyltransferase (NNMT) is overexpressed in EC, especially in EC, and predicts poor survival of chemotherapy patients. Here, we aimed to determine the function and mechanism of NNMT on metastasis of EC. Additionally, analysis of public datasets indicated that NNMT is involved in cholesterol metabolism. In vitro, NNMT overexpression promoted migration and invasion of EC by reducing cholesterol levels in the cytoplasm and cell membrane. Mechanistically, NNMT activated ABCA1 expression, leading to cholesterol efflux and membrane fluidity enhancement, thereby promoting EC's epithelial-mesenchymal transition (EMT). In vivo, the metastasis capacity of EC was weakened by targeting NNMT. Our findings suggest a new molecular mechanism involving NNMT in metastasis, poor survival of EC mediated by PP2A and affecting cholesterol metabolism.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Endométrio
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Fluidez de Membrana
Limite:
Female
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article