Breast cancer secretes anti-ferroptotic MUFAs and depends on selenoprotein synthesis for metastasis.
Breast Cancer
Ferroptosis
Lipid Metabolism
Metastasis
Selenium Metabolism
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: Germany
ID NLM: 101487380
Informations de publication
Date de publication:
21 Oct 2024
21 Oct 2024
Historique:
received:
23
06
2023
accepted:
04
09
2024
revised:
23
08
2024
medline:
22
10
2024
pubmed:
22
10
2024
entrez:
21
10
2024
Statut:
aheadofprint
Résumé
The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate of metastatic recurrence and poor prognosis. Ferroptosis is a type of cell death caused by iron-dependent lipid peroxidation and counteracted by the antioxidant activity of the selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in the extracellular environment when cultured at high cell densities but are primed to ferroptosis when forming colonies at low density. We found that secretion of the anti-ferroptotic factors, identified as monounsaturated fatty acid (MUFA) containing lipids, and the vulnerability to ferroptosis of single cells depends on the low expression of stearyl-CoA desaturase (SCD) that is proportional to cell density. Finally, we show that the inhibition of Sec-tRNAsec biosynthesis, an essential step for selenoprotein production, causes ferroptosis and impairs the lung seeding of circulating TNBC cells that are no longer protected by the MUFA-rich environment of the primary tumour.
Identifiants
pubmed: 39433871
doi: 10.1038/s44321-024-00142-x
pii: 10.1038/s44321-024-00142-x
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Cancer Research UK (CRUK)
ID : A31287
Organisme : Cancer Research UK (CRUK)
ID : A29800
Organisme : Cancer Research UK (CRUK)
ID : A29799
Organisme : Cancer Research UK (CRUK)
ID : A23982
Organisme : Breast Cancer Now (BCN)
ID : 2018NovPR102
Informations de copyright
© 2024. The Author(s).
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