Induction of stearoyl-CoA desaturase confers cell density-dependent ferroptosis resistance in melanoma.
ferroptosis
glutathione peroxidase 4
melanoma
stearoyl-CoA desaturase
Journal
Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768
Informations de publication
Date de publication:
16 Feb 2024
16 Feb 2024
Historique:
revised:
18
01
2024
received:
20
10
2023
accepted:
06
02
2024
medline:
16
2
2024
pubmed:
16
2
2024
entrez:
16
2
2024
Statut:
aheadofprint
Résumé
Ferroptosis is a form of regulated cell death that is induced by inhibiting glutathione peroxidase 4 (GPX4), which eliminates lipid peroxidation. Ferroptosis induction is influenced by the cell environment. However, the cellular states altering ferroptosis susceptibility remain largely unknown. We found that melanoma cell lines became resistant to ferroptosis as cell density increased. Comparative transcriptome and metabolome analyses revealed that cell density-dependent ferroptosis resistance was coupled with a shift toward a lipogenic phenotype accompanied by strong induction of stearoyl-CoA desaturase (SCD). Database analysis of gene dependency across hundreds of cancer cell lines uncovered a negative correlation between GPX4 and SCD dependency. Importantly, SCD inhibition, either pharmacologically or through genetic knockout, sensitized melanoma cells to GPX4 inhibition, thereby attenuating ferroptosis resistance in cells at high density. Our findings indicate that transition to an SCD-inducing, lipogenic cell state produces density-dependent resistance to ferroptosis, which may provide a therapeutic strategy against melanoma.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : JSPS KAKENHI
ID : 21K15539
Organisme : JSPS KAKENHI
ID : 22H02932
Organisme : Nippon Foundation
Organisme : Takeda Science Foundation
Informations de copyright
© 2024 Wiley Periodicals LLC.
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