Tissue Factor Pathway Inhibitor 2 Enhances Hepatocellular Carcinoma Chemosensitivity by Activating CCAR2-GADD45A-Mediated DNA Damage Repair.

ABSTRACT: Chemotherapy resistance presents a major challenge in the treatment of hepatocellular carcinoma (HCC), with the underlying molecular mechanisms largely unknown. This study aimed to investigate the role of tissue factor pathway inhibitor 2 (TFPI2) in modulating HCC chemosensitivity. We explored the impact of TFPI2 on sorafenib sensitivity in patient-derived organoids and mouse models using immunofluorescence analysis, chromatin immunoprecipitation, and RNA immunoprecipitation. We observed the downregulation of TFPI2 in HCC, and its deletion in mice (TFPI2^HKO) accelerated DEN-induced liver tumorigenesis. Notably, TFPI2 overexpression increased sorafenib sensitivity in HCC organoids and in vivo models. Mechanistic insights indicated that TFPI2 stabilizes the mRNA of growth a

SUBMITTER: Zhou H 

PROVIDER: S-EPMC12320495 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature