Late SV40 factor: A key mediator of Notch signaling in human hepatocarcinogenesis

摘要

AIM: To investigate the relationship between late SV40 factor (LSF) and Notch signaling in the development and progress of hepatocellular carcinoma (HCC).METHODS: Liver cancer tissue specimens from 25 patients were analyzed for Notch-1 and LSF expression by immunohistochemistry. The correlation between expression and the biological effects of Notch-1 and LSF were analyzed using genetic and pharmacological strategies in HCC cell lines and human normal cell lines, including hepatic stellate cells (HSC) and human embryonic kidney epithelial cells (HEK).RESULTS: Immunohistochemistry showed that both Notch-1 and LSF were significantly upregulated in HCC samples (76%, 19/25, P < 0.0001 and 84%, 21/25, P < 0.0001, respectively) compared with non-cancer samples. Activation of Notch-1 by exogenous transfection of Notch1 intracellular domain increased LSF expression in HSC and HEK cells to levels similar to those seen in HepG2 cells. Furthermore, blocking Notch-1 activation with a γ-secretase inhibitor, DAPT, downregulated LSF expression in HepG2 cells. Additionally, a biological behavior assay showed that forced overexpression of LSF promoted HepG2 cell proliferation and invasion.CONCLUSION: LSF is a key mediator of the Notch signaling pathway, suggesting that it might be a novel therapeutic target for the treatment of HCC.