On February 17, the research teams led by Yan-Dong Wang from College of Life Science and Technology, Beijing University of Chemical Technology, in collaboration with Wei-Dong Chen from School of Basic Medical Science, Inner Mongolia Medical University, published a paper titled "Targeting tRNA-dependent tyrosine usage unveils a metabolic vulnerability in hepatocellular carcinoma" in Nature Communications (IF=15.7).
Cancer cells reprogram translation and metabolism to fuel tumorigenesis. In hepatocellular carcinoma (HCC), tyrosine is paradoxically maintained at low levels yet preferentially directed to translation via MYC-driven upregulation of YARS1 and tRNA-TyrGUA.
Key findings:
3.Genome-wide CRISPR screening reveals that loss of GPX4 or BCL2 genetically or pharmacologically enhances the anti-tumor efficacy of RTTA.
This study establishes RTTA as a therapeutic strategy targeting tyrosine dependency and highlights combinatorial targeting of translation-metabolism crosstalk and ferroptosis pathways in liver cancer. Ribosome profiling (Ribo-seq) and RNA-seq for this research were conducted on the GeneMind SURFSeq 5000 platform.
