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Targeting tRNA-dependent tyrosine usage unveils a metabolic vulnerability in hepatocellular carcinoma

ABSTRACT: proteomics and metabolomics analysis of HCC cells cultured in tyrosine deprived medium

ORGANISM(S): Homo Sapiens

SUBMITTER: Yandong Wang

PROVIDER: PXD072551 | iProX | Tue Dec 30 00:00:00 GMT 2025

REPOSITORIES: iProX

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Targeting tRNA-dependent tyrosine usage unveils a metabolic vulnerability in hepatocellular carcinoma.

Zhang Hongli H Wang Zixuan Z Zhao Yiqi Y Deng Xiya X Zhang Jian J Shang Fei F Zhang Hongjie H Liu Yan Y Wang Hongbo H Yang Yating Y Lin Huiyu H Zhang Bo B Liu Ce C Guo Fan F Zhang Ruolin R Yuan Qipeng Q Feng Yue Y Luo Shi-Zhong SZ Chen Wei-Dong WD Wang Yan-Dong YD

Nature communications 20260306 1

Cancer cells reprogramme translation and metabolism to fuel tumorigenesis. Here, we show that hepatocellular carcinoma (HCC) paradoxically maintains low tyrosine levels despite increased uptake and reduced metabolism, redirecting tyrosine to translation via MYC-driven upregulation of tyrosyl-tRNA synthetase 1 (YARS1) and tRNA-Tyr<sup>GUA</sup>. Restricting tyrosine translation availability (RTTA) via dietary limitation, YARS1/tRNA-Tyr<sup>GUA</sup> ablation, tyrosine degradation (TAL), or YARS1 ...[more]

PMID: 41792125

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