β-catenin mutation reprograms ketone body metabolism to drive hepatocellular carcinoma metastasis and resistance to ketogenic therapy via transcriptional activation of OXCT1 - PubMed
3 days ago
- #ketogenic therapy resistance
- #β-catenin mutation
- #hepatocellular carcinoma
- β-catenin mutation (S33Y) in hepatocellular carcinoma (HCC) leads to resistance to ketogenic therapy and promotes metastasis.
- OXCT1, a key enzyme in ketone body catabolism, is aberrantly activated by mutated β-catenin, driving ketolysis and metabolic reprogramming.
- Blocking OXCT1 in β-catenin-mutated HCC reverses ketogenic therapy resistance and reduces metastasis by lowering tumor glutamate levels.
- OXCT1 activation enhances HCC metastasis via p-STAT3 and epithelial-mesenchymal transition pathways.
- Targeting OXCT1 presents a potential therapeutic strategy for β-catenin-mutated HCC.