CtBP2 was initially discovered as a phosphoprotein bound to the C-terminal of the adenovirus E1A protein. It was recently reported to function as a transcriptional co-repressor that binds various transcriptional repressors with PXDLS binding motifs. In turn, these transcriptional repressors target and suppress the expression of multiple tumor repressors, including E-cadherin [31], PTEN [32] and p16Ink4a [33]. Using both in vitro and in vivo experiments, we demonstrated that CtBP2 overexpression induced EMT in HCC and promoted cell migration and invasion. After searching the RCSB Protein Data Bank, we found that the SNAI1 protein contained the PQDLSLK motif. The presence of this motif implied that the CtBP2 protein was potentially a binding partner of the SNAI1 protein and that CtBP2 might function as a transcriptional co-repressor. The Co-IP results confirmed this hypothesis. Additionally, the in vitro experiments revealed that CtBP2 knockdown reversed GLI1/SNAI1 driven EMT, but CtBP2 could not induce EMT in HCC cells without SNAI1 expression. Interestingly, we found that enhanced GLI1 expression promoted CtBP2 upregulation. Fourteen potential GLI1-binding sites were observed in the CtBP2 promoter after searching the RCSB
