Open access
Jul 2026
AARS1-catalyzed H4K12 lactylation promotes HCC resistance to targeted therapy by activating RAPGEF3-RAP1 signaling.
A novel metabolic-epigenetic mechanism whereby lactate modulates hepatocellular carcinoma sensitivity to targeted therapies through histone lactylation is delineated and suggests AARS1-H4K12la-RAPGEF3 axis may serve as an interventional target to overcome targeted drug resistance, offering a promising strategy to enhance clinical outcomes in HCC patients.
Tanlun Zeng, Wanwan Zhu, Guanqun Sun et al.
· Cell Death and Disease · 1 citation