Tissue factor promotes vascular invasion and metastasis in hepatocellular carcinoma via combined activation of β-catenin/STAT3 signaling - PubMed
3 hours ago
- #hepatocellular carcinoma
- #tissue factor
- #metastasis
- Tissue factor (TF) is upregulated in hepatocellular carcinoma (HCC) and linked to poor prognosis.
- Overexpression of TF enhances HCC cell proliferation, migration, invasion, and spheroid formation in vitro, and promotes tumor growth and metastasis in vivo.
- High TF expression increases the dissemination of circulating tumor cells (CTCs) and circulating tumor microemboli (CTMs), facilitating hematogenous spread.
- Mechanistically, TF activates PAR1, leading to activation of Wnt/β-catenin and JAK2/STAT3 pathways, with nuclear translocation of β-catenin and STAT3.
- Nuclear STAT3 enhances TF promoter activity, creating a positive feedback loop that sustains downstream signaling.
- Combined inhibition of TF with β-catenin and STAT3 blockers effectively suppresses HCC tumorigenesis and metastasis.