title: TAZ regulates cell proliferation and epithelial-mesenchymal transition of human hepatocellular carcinoma.
abstract: The transcriptional coactivator with PDZ binding motif (TAZ) has been reported to be one of the nuclear effectors of Hippo-related pathways. TAZ is expressed in many primary tumors and could regulate many biological processes. However, little is known about the role of TAZ in hepatocellular carcinoma (HCC). In the current study, we show that TAZ regulates cellular proliferation and epithelial-mesenchymal transition (EMT) of HCC. TAZ is overexpressed in HCC tissues and cell lines and upregulation of TAZ correlates with a lower overall survival rate of HCC patients after hepatic resection. TAZ knockdown results in inhibition of cancer cell proliferation through decreases in expression of stem cell markers (OCT4, Nanog, and SOX2). Reduction in HCC cell migration and invasion is also evident through reversal of EMT by increases E-cadherin expression, decreases in N-cadherin, vimentin, Snail, and Slug expression, and suppression of MMP-2 and MMP-9 expression. In a xenograft tumorigenicity model, TAZ knockdown could effectively inhibit tumor growth and metastasis through reversal of the EMT pathway. In conclusion, TAZ is associated with the proliferation and invasiveness of HCC cells, and the TAZ gene may contribute to a novel therapeutic approach against HCC.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xiao
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.forename: Baoyong
authors.initials: B
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.forename: Chengyou
authors.initials: C
authors.lastname: Du
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D018398:Homeodomain Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D055748:SOXB1 Transcription Factors; D015398:Signal Transduction / Q000235:genetics; D000071250:Snail Family Transcription Factors; D013234:Stem Cells / Q000378:metabolism; D015996:Survival Rate; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D015854:Up-Regulation / Q000235:genetics; D014746:Vimentin / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000604407:SNAI1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000091364:Transcriptional Coactivator with PDZ-Binding Motif Proteins; D014746:Vimentin; C551991:WWTR1 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Cancer stem cell; TAZ; cell proliferation; epithelial-mesenchymal transition (EMT); human hepatocellular carcinoma (HCC)