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FSP1 and histone deacetylases suppress cancer persister cell ferroptosis

GSE303411 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/11/10 Platform GPL24676
Summary
Cancer persister cells which survive oncogene targeted therapies are sensitized to ferroptosis but mechanistic understanding of this vulnerability remains limited. Here, we found that while levels of iron, glutathione and various ferroptosis suppressing enzymes vary among persister cell types, ferroptosis suppressor protein 1 (FSP1) is downregulated in multiple persister cell types and persister cells which survive glutathione peroxidase 4 (GPX4) inhibition rely upon residual FSP1 to survive. Furthermore, persister cells which survive GPX4 inhibition downregulate oxidative phosphorylation, a key source of mitochondrial reactive oxygen species which are required for persister cell ferroptosis. We also found that persister cell treatment with histone deacetylase inhibitors induce reactive oxygen species and sensitize multiple persister cell types to GPX4 inhibition. Together, these findings reveal that FSP1 and histone deacetylases suppress persister cell ferroptosis.
Published in
FSP1 and histone deacetylases suppress cancer persister cell ferroptosis
Higuchi M, Williams AF, Stuhlfire AE et al. · Science advances 2026 · PMID 41481741 · doi:10.1126/sciadv.aea8771
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Also filed as BioProject PRJNA1295369 and SRA study SRP602927. Searching any of these in the dataset finder brings you back here.

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