ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer.
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.
Lin
Li-Fang
LF
Institute of Basic Medical Sciences, National Cheng Kung University, Department of Pathology, Tainan, Taiwan.
Chuang
Chih-Hung
CH
Li
Chien-Feng
CF
Liao
Ching-Chun
CC
Cheng
Chun-Pei
CP
Cheng
Tian-Lu
TL
Shen
Meng-Ru
MR
Tseng
Joseph T
JT
Chang
Wen-Chang
WC
Lee
Wen-Hwa
WH
Wang
Ju-Ming
JM
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*
D012097:Repressor Proteins; C422407:ZNF350 protein, human; D020780:Matrix Metalloproteinase 9