Ly96-mediated activation of TGF-β1/Smad2/3 signaling in hepatocellular carcinoma and its potential for nanoparticle-based therapy

• LY96 is significantly overexpressed in HCC tissues and correlates with poor overall survival, indicating its potential as a prognostic biomarker. • Mechanistically, LY96 promotes HCC progression by activating the TGF-β1/Smad2/3 signaling pathway, as confirmed by in vitro and in vivo experiments. • A novel liposome-based nanoparticle system delivering the LY96 inhibitor L6H21 effectively suppresses HCC growth, offering a promising targeted therapeutic strategy. • The study integrates bioinformatics, experimental validation, and nanomedicine to identify and therapeutically target a key molecular driver in HCC.