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Induction of stearoyl-CoA desaturase confers cell density-dependent ferroptosis resistance in melanoma.

Authors :
Shirahama H
Tani Y
Tsukahara S
Okamoto Y
Hasebe A
Noda T
Ando S
Ushijima M
Matsuura M
Tomida A
Source :
Journal of cellular biochemistry [J Cell Biochem] 2024 Apr; Vol. 125 (4), pp. e30542. Date of Electronic Publication: 2024 Feb 16.
Publication Year :
2024

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.<br /> (© 2024 Wiley Periodicals LLC.)

Details

Language :
English
ISSN :
1097-4644
Volume :
125
Issue :
4
Database :
MEDLINE
Journal :
Journal of cellular biochemistry
Publication Type :
Academic Journal
Accession number :
38362828
Full Text :
https://doi.org/10.1002/jcb.30542