ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer

Li Fang Lin; Chih Hung Chuang; Chien Feng Li; Ching Chun Liao; Chun Pei Cheng; Tian Lu Cheng; Meng Ru Shen; Joseph T. Tseng; Wen Chang; Wen Hwa Lee; Ju Ming Wang

doi:10.1158/0008-5472.CAN-09-2641

ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer

Li Fang Lin, Chih Hung Chuang, Chien Feng Li, Ching Chun Liao, Chun Pei Cheng, Tian Lu Cheng, Meng Ru Shen, Joseph T. Tseng, Wen Chang, Wen Hwa Lee, Ju Ming Wang

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

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.

Original language	English
Pages (from-to)	192-201
Number of pages	10
Journal	Cancer Research
Volume	70
Issue number	1
DOIs	https://doi.org/10.1158/0008-5472.CAN-09-2641
Publication status	Published - Jan 1 2010

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/0008-5472.CAN-09-2641

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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.",

author = "Lin, {Li Fang} and Chuang, {Chih Hung} and Li, {Chien Feng} and Liao, {Ching Chun} and Cheng, {Chun Pei} and Cheng, {Tian Lu} and Shen, {Meng Ru} and Tseng, {Joseph T.} and Wen Chang and Lee, {Wen Hwa} and Wang, {Ju Ming}",

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AU - Lin, Li Fang

AU - Chuang, Chih Hung

AU - Li, Chien Feng

AU - Liao, Ching Chun

AU - Cheng, Chun Pei

AU - Cheng, Tian Lu

AU - Shen, Meng Ru

AU - Tseng, Joseph T.

AU - Chang, Wen

AU - Lee, Wen Hwa

AU - Wang, Ju Ming

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

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ZBRK1 acts as a metastatic suppressor by directly regulating MMP9 in cervical cancer

Abstract

ASJC Scopus subject areas

UN SDGs

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