SIRT3 deacetylates STEAP4 to modulate cuproptosis sensitivity via mitochondrial metabolic reprogramming in HBV-related HCC - PubMed
5 hours ago
- #Cuproptosis
- #HBV-related HCC
- #Metabolic reprogramming
- HBV infection is a leading cause of hepatocellular carcinoma (HCC).
- Cuproptosis is a copper-dependent cell death mechanism targeting mitochondria-dependent cells.
- HBV X protein (HBx) downregulates STEAP4, reducing cuproptosis sensitivity in HBV-related HCC.
- HBx attenuates SIRT3, impairing STEAP4 deacetylation and mitochondrial targeting.
- This metabolic shift from TCA cycle to glycolysis reduces sensitivity to copper ionophore elesclomol (ES).
- Restoring STEAP4 or activating SIRT3 with honokiol (HKL) re-sensitizes cells to cuproptosis.
- Combination therapy with ES shows synergistic tumor suppression in HBV-related HCC models.
- The SIRT3-STEAP4 axis is a key regulator of cuproptosis resistance in HBV-related HCC.