CtBP2 is an independent prognostic marker that promotes GLI1 induced epithelial-mesenchymal transition in hepatocellular carcinoma

Oncotarget. 2015 Feb 28;6(6):3752-69. doi: 10.18632/oncotarget.2915.


C-terminal binding protein 2 (CtBP2) is a transcriptional co-repressor that promotes cancer cell migration and invasion by inhibiting multiple tumor suppressor genes that contribute to cell mobility and adhesion. In this investigation, we showed thatCtBP2 expression was increased significantly in HCC tissues when compared to matched normal adjacent liver tissues. We also showed that CtBP2 expression is associated with worse HCC patient prognosis after liver resection. CtBP2 over-expression induced epithelial-mesenchymal transition (EMT) in Huh7 cells and, correspondingly, silencing CtBP2 suppressed EMT in MHCC97H cells. ChIP assays revealed that GLI1 increased CtBP2 transcription by directly binding its promoter. Furthermore, interaction of CtBP2 and Snail Family Zinc Finger 1 (SNAI1), both of which were found to be positively regulated by GLI1, was confirmed by Co-IP assay. SNAI1 knockdown revealed that SNAI1 was essential for CtBP2 induction of the EMT phenotype of HCC cells, and CtBP2 knockdown reversed GLI1-SNAI1 driven EMT in Huh7 cells. Finally, in vivo experiments demonstrated that enhanced CtBP2expression promoted HCC xenograft growth and induced EMT. In conclusion, CtBP2 may serve as a prognostic marker for post liver resection HCC and may play a role during GLI1-driven EMT as a transcriptional co-repressor of SNAI1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / biosynthesis*
  • Alcohol Oxidoreductases / genetics
  • Animals
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Co-Repressor Proteins
  • Epithelial-Mesenchymal Transition
  • Female
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Prognosis
  • Snail Family Transcription Factors
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Zinc Finger Protein GLI1


  • Biomarkers, Tumor
  • Co-Repressor Proteins
  • GLI1 protein, human
  • Nerve Tissue Proteins
  • SNAI1 protein, human
  • Snai1 protein, mouse
  • Snail Family Transcription Factors
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • Alcohol Oxidoreductases
  • CTBP2 protein, human