title: CtBP1 is involved in epithelial-mesenchymal transition and is a potential therapeutic target for hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a highly invasive type of cancer. Metastasis is the leading cause of mortality of advanced HCC patients. In the metastasis cascade, cancer cells undergo epithelial-mesenchymal transition resulting in the loss of cell‑to‑cell adhesion, migration and invasion into the stroma. Loss of E-cadherin expression is a key molecular event in epithelial-mesenchymal transition through several regulatory mechanisms including epigenetic modification, regulation by inhibitory transcriptional factors and deletion of chromosome 16q24 locus. C-terminal binding protein 1 (CtBP1) functions as a corepressor binding to several transcriptional factors and suppresses E-cadherin expression. We found that CtBP1 was upregulated in HCC when compared with paired normal liver tissues and was inversely correlated with E-cadherin expression in HCC by immunohistochemical assay using tissue array. Western blot analysis confirmed the results of the immunohistochemical assays. When CtBP1 was knocked down by siRNA in HepG2 cells (a human HCC cell line), E-cadherin was upregulated and the invasive ability of HepG2 cells was inhibited. In addition, following CtBP1 knockdown, the cell viability was decreased along with increased apoptosis rather than cell cycle arrest. These data suggest a pivotal role of CtBP1 in EMT of HCC, and its potential as a therapeutic target in human disease.
authors.affiliation: GuangXi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, PR China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zhang
authors.forename: Cheng-Xin
authors.initials: CX
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Akira
authors.initials: A
authors.lastname: Inoue
authors.forename: Si-En
authors.initials: SE
authors.lastname: Zeng
authors.forename: Sheng-Jun
authors.initials: SJ
authors.lastname: Xiao
mesh_terms: D000328:Adult; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015854:Up-Regulation
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein