CtBP2 is an independent prognostic marker that promotes GLI1 induced epithelial-mesenchymal transition in hepatocellular carcinoma
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Xin Zheng1,*, Tao Song1,*, Changwei Dou1, Yuli Jia1, Qingguang Liu1
1Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China
*These authors have contributed equally to this work
Qingguang Liu, e-mail: email@example.com
Keywords: C-terminal binding protein 2, GLI family zinc finger 1, Snail Family Zinc Finger 1, epithelialmesenchymal transition, Hepatocellular carcinoma
Received: November 12, 2014 Accepted: December 15, 2014 Published: February 26, 2015
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.
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