L-lactate-driven PSMD14 lactylation and stabilization promote lactate production and ferroptosis resistance via ENO1 in intrahepatic cholangiocarcinoma - PubMed
3 days ago
- #ICC
- #glycolysis
- #ferroptosis
- Targeting ferroptosis is a promising treatment strategy for intrahepatic cholangiocarcinoma (ICC).
- A novel ferroptosis resistance score (FRS) was developed to assess ICC samples.
- Glycolysis is closely associated with FRS, and L-lactate drives ferroptosis resistance via PSMD14.
- L-lactate promotes PSMD14 lactylation, delaying its degradation and stabilizing ENO1.
- PSMD14 interacts with ENO1, reducing its ubiquitination and inhibiting lysosomal degradation.
- Targeting PSMD14 inhibits L-lactate production and ferroptosis resistance, enhancing anti-PD-1 efficacy.
- High expression of PSMD14 and ENO1 in ICC tumors correlates with poor prognosis.
- The L-lactate/PSMD14/ENO1 axis is crucial for ferroptosis resistance in ICC.