RNF26 regulating tumor immunogenicity of hepatocellular carcinoma by degrading GRP78 and instigating ER stress - PubMed
7 days ago
- #ER Stress
- #Immune Resistance
- #Hepatocellular Carcinoma
- RNF26 is highly expressed in immune-'cold' hepatocellular carcinoma (HCC) and is regulated by the JAK-STAT3 inflammatory axis.
- RNF26 degrades the ER chaperone GRP78 via K48-linked polyubiquitination, leading to sustained ER stress in HCC cells.
- ER stress caused by RNF26 results in reduced MHC-I antigen presentation and increased PD-L1 expression, promoting immune evasion.
- RNF26-mediated ER stress inhibits CD8+ T cell infiltration and promotes T cell exhaustion, contributing to immune resistance in HCC.
- Targeting the RNF26-GRP78 axis could be a novel strategy to reverse HCC immune resistance and improve immunotherapy efficacy.