title: ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.
abstract: The BRCA1-interacted transcriptional repressor ZBRK1 has been associated with antiangiogenesis, but direct evidence of a tumor suppressor role has been lacking. In this study, we provide evidence of such a role in cervical carcinoma. ZBRK1 levels in cervical tumor cells were significantly lower than in normal cervical epithelial cells. In HeLa cervical cancer cells, enforced expression inhibited malignant growth, invasion, and metastasis in a variety of in vitro and in vivo assays. Expression of the metalloproteinase MMP9, which is known to be an important driver of invasion and metastasis, was found to be inversely correlated with ZBRK1 in tumor tissues and a target for repression in tumor cells. Our findings suggest that ZBRK1 acts to inhibit metastasis of cervical carcinoma, perhaps by modulating MMP9 expression.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Department of Pathology, Tainan, Taiwan.
authors.forename: Li-Fang
authors.initials: LF
authors.lastname: Lin
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Chuang
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Ching-Chun
authors.initials: CC
authors.lastname: Liao
authors.forename: Chun-Pei
authors.initials: CP
authors.lastname: Cheng
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Shen
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Tseng
authors.forename: Wen-Chang
authors.initials: WC
authors.lastname: Chang
authors.forename: Wen-Hwa
authors.initials: WH
authors.lastname: Lee
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D006801:Humans; D047468:Immunoprecipitation; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
chemical_list: D012097:Repressor Proteins; C422407:ZNF350 protein, human; D020780:Matrix Metalloproteinase 9