Targeting tRNA-dependent tyrosine usage unveils a metabolic vulnerability in hepatocellular carcinoma - PubMed
5 days ago
- #tyrosine metabolism
- #hepatocellular carcinoma
- #ferroptosis
- Hepatocellular carcinoma (HCC) maintains low tyrosine levels despite increased uptake and reduced metabolism.
- MYC-driven upregulation of YARS1 and tRNA-TyrGUA redirects tyrosine to translation in HCC.
- Restricting tyrosine translation availability (RTTA) mitigates tumorigenesis and extends survival.
- RTTA reduces tyrosine codon-dependent translation of NDUFB8 and SCD1, leading to complex I misassembly and ferroptosis.
- CRISPR screening identifies GPX4 and BCL2 loss enhances RTTA's ability to inhibit HCC.
- RTTA is a therapeutic strategy targeting tyrosine dependency in liver cancer.