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

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 aγ-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.