We have identified a role for CtBP2 in the progression of HCC and revealed a correlation between CtBP2 expression in HCC tissues and patient prognosis after liver resection. We report six novel discoveries in this study: (1) CtBP2 was upregulated in HCC tissues when compared to matched adjacent healthy liver tissues and CtBP2 overexpression in HCC tissues was correlated with poor patient prognosis; (2) CtBP2 overexpression promoted cell motility and invasion by inducing EMT in HCC cells; (3) GLI1 bound the CtBP2 promoter directly and increased its expression, which is potentially the underlying mechanism of CtBP2 upregulation in HCC; (4) CtBP2 bound SNAI1, a well-known EMT inducer, and was required as a transcriptional co-repressor for GLI1/SNAI1 driven EMT in HCC cells; (5) SNAI1 was also essential for CtBP2 induced EMT in HCC cells; (6) CtBP2 overexpression accelerated tumor growth and promoted EMT in HCC xenograft tumors. In summary, the results of this study strongly support the potential of CtBP2 as a predictive factor of patient outcome after liver resection and as a therapeutic target for the treatment of HCC.
