Activation of methionine metabolism mediated by HNF4α confers ferroptosis resistance in hepatocellular carcinoma - PubMed
5 hours ago
- #ferroptosis
- #HNF4α
- #methionine metabolism
- Ferroptosis induction is a promising therapeutic strategy for hepatocellular carcinoma (HCC), but its efficacy is limited by tumor heterogeneity.
- Epithelial HCC cells (EC) show resistance to ferroptosis, linked to the cysteine and methionine metabolic pathway.
- Transcriptomics and metabolomics analyses reveal that methionine metabolism is crucial for EC resistance to ferroptosis inducer IKE.
- Inhibiting key methionine metabolic enzymes increases cell death and oxidative stress in EC.
- HNF4α transcriptionally regulates major methionine metabolic enzymes, enhancing cellular antioxidant capacity.
- Down-regulation of HNF4α abolishes ferroptosis resistance in both in vitro experiments and in vivo mouse models.
- HNF4α and methionine metabolic enzymes are potential therapeutic targets to overcome ferroptosis resistance in HCC.