Induction of stearoyl-CoA desaturase confers cell density-dependent ferroptosis resistance in melanoma.
J Cell Biochem
; 125(4): e30542, 2024 04.
Article
en En
| MEDLINE
| ID: mdl-38362828
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_malignant_skin_melanoma
Asunto principal:
Estearoil-CoA Desaturasa
/
Ferroptosis
/
Melanoma
Límite:
Humans
Idioma:
En
Revista:
J Cell Biochem
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón