title: Snail1-dependent transcriptional repression of Cezanne2 in hepatocellular carcinoma.
abstract: High malignancy and early metastasis are the hallmarks of hepatocellular carcinoma (HCC). Here, we report that Cezanne2 expression is downregulated in HCC cells and in HCC patients' tumorous tissues and that Cezanne2 is inversely associated with Snail1 expression in HCC patients' tumorous tissues. Chromatin immunoprecipitation assays and the reporter gene assay showed that Snail1 binds to the promoter of the Cezanne2 gene and mediates the direct consequence of Cezanne2 repression. Enhanced expression of Cezanne2 could suppress proliferation, migration and invasion in HCC cells. Further, Cezanne2 could regulate MMP (matrix metalloproteinase)2, MMP9 and ICAM1 (intercellular adhesion molecule) levels through modulation of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cell) signaling cascade. Co-immunoprecipitation and in vivo deubiquitination assay indicated that Cezanne2 interacts with TNF receptor-associated factor (TRAF)6 and cleaves the polyubiquitin from TRAF6 substrates. Our data reveal that Snail1-mediated suppression of Cezanne2 may have a key role in HCC malignancy.
authors.affiliation: Department of molecular diagnosis, ZhongCheng Translational-Medicine Inc, Shanghai, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of molecular diagnosis, ZhongCheng Translational-Medicine Inc, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Pei
authors.affiliation: School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of molecular diagnosis, ZhongCheng Translational-Medicine Inc, Shanghai, China.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.affiliation: Sir Run Run Shaw Hospital, Affiliated with School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Gui
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D000072017:Deubiquitinating Enzymes; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D048029:TNF Receptor-Associated Factor 6 / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D054875:Ubiquitination
chemical_list: D016328:NF-kappa B; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D048029:TNF Receptor-Associated Factor 6; D014157:Transcription Factors; D018799:Intercellular Adhesion Molecule-1; D010450:Endopeptidases; D000072017:Deubiquitinating Enzymes; C000629287:OTUD7A protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9