Cathepsin-facilitated invasion of BMI1-high hepatocellular carcinoma cells drives bile duct tumor thrombi formation.

ABSTRACT: Bile duct tumor thrombosis (BDTT) is a complication mostly observed in patients with advanced hepatocellular carcinoma (HCC), causing jaundice and associated with poor clinical outcome. However, its underlying molecular mechanism is unclear. Here, we develop spontaneous preclinical HCC animal models with BDTT to identify the role of BMI1 expressing tumor initiating cells (BMI1^high TICs) in inducing BDTT. BMI1 overexpression transforms liver progenitor cells into BMI1^high TICs, which possess strong tumorigenicity and increased trans-intrahepatic biliary epithelial migration ability by secreting lysosomal cathepsin B (CTSB). Orthotopic liver implantation of BMI1^high TICs into mice generates tumors and triggers CTSB mediated bile duct invasion to form tumor th

SUBMITTER: Xu LB 

PROVIDER: S-EPMC10624910 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature