Alisertib impairs the stemness of hepatocellular carcinoma by inhibiting purine synthesis.

ABSTRACT: Hepatocellular carcinoma tumor-repopulating cells (HCC-TRCs) drive disease progression, yet their purine metabolism mechanisms remain poorly understood. This study revealed that the stemness index, strongly linked to poor HCC prognosis, exhibited a robust positive correlation with purine metabolism through single-sample gene set enrichment analysis. Integrated drug screening across CTRP, GDSC, and PRISM databases identified alisertib, an aurora kinase A (AURKA) inhibitor, as a potent agent targeting stemness. Using fibrin gel-based 3D-cultured HCC-TRCs, mechanistic studies demonstrated that alisertib suppresses xanthine and hypoxanthine production by inhibiting the AURKA-AKT signaling axis. This disruption markedly impaired tumor spheroid formation, migration, and invasion in vitro, while

SUBMITTER: Qi Z 

PROVIDER: S-EPMC12152889 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature