Abstract

BACKGROUND: The C-terminus of E1A binding proteins (CTBPs) has recently been shown to stimulate tumorigenesis in several human tissues by participating in cell signal transduction. However, to date, the expression profile of CTBP isoforms in hepatocellular carcinoma (HCC) and the impact of CTBPs on HCC cell phenotype have not been fully explored.

MATERIAL AND METHODS: The expression level of CTBP1 was investigated in various HCC cell lines and HCC tissues by RT-qPCR, Western blotting, and immunohistochemistry assays. The phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 was utilized to treat hepatic astrocyte cells, and the impact of CTBP1 on proliferation and metastasis of hepatic astrocytes and HCC cells was accessed by CCK-8, clone-forming, Transwell chamber, and cell scratch assays.

RESULTS: Increased expression of CTBP1 was observed in HCC tissues and was a predictor of poor prognosis in HCC patients. CTBP1 modified proliferation and migratory activity of HCC cells via the PI3K/protein kinase B (Akt) signaling pathway in hepatic astrocytes. Moreover, genetic loss of CTBP1 significantly reduced the metastatic activity of HCC cells in vitro.

CONCLUSIONS: Our data suggest that the loss of CTBP1 suppresses cell proliferative and invasive activity of HCC cells via the PI3K/Akt pathway.

Keywords: Carcinoma, Hepatocellular, Genes, Tumor Suppressor, Intracellular Signaling Peptides and Proteins, Aged, Alcohol Oxidoreductases, Apoptosis, Cell Movement, Cell Proliferation, Chromones, DNA-Binding Proteins, Liver Neoplasms, Middle Aged, Morpholines, Neoplasm Invasiveness, Neoplasm Metastasis, Phenotype, phosphatidylinositol 3-kinase, Phosphoinositide-3 Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Signal Transduction