Localization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells

Guangli Wang, Yao Zeng, Shaoying Chen, Deling Li, Wei Li, Yanchun Zhou, Robert H. Singer, Wei Gu

Research output: Contribution to journalArticle

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Abstract

TFPI-2 has recently been recognized as a tumor suppressor, which not only plays a fundamental role in modulation of ECM integrity, but also involves the regulation of many oncogenes. In this study, we investigated the potential mechanism of TFPI-2 in the suppression of breast cancer growth and invasion. We showed that, with either over-expression of TFPI-2 or after treatment with exogenous rTFPI-2, breast cancer cells exhibited reduced proliferation and invasion. We demonstrated that in addition to being secreted, TFPI-2 was also distributed throughout the cytoplasm and nucleus. Nuclear localization of TFPI-2 contributed to inhibition of MMP-2 mRNA expression, which could be reversed after the nuclear localization signal was deleted. In the nucleus, interaction of TFPI-2 with Ap-2α attenuated the binding of AP-2α to the MMP-2 promoter, therefore reducing the transcriptional activity of the gene. Our results suggest that one of the mechanisms by which TFPI-2 inhibits breast cancer cell invasion could be via the regulation of MMP-2 gene transcription.

Original languageEnglish (US)
Article number13575
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Matrix Metalloproteinases
Breast Neoplasms
Gene Expression
Nuclear Localization Signals
tissue-factor-pathway inhibitor 2
Oncogenes
Genes
Cytoplasm
Messenger RNA
Growth
Neoplasms

ASJC Scopus subject areas

  • General

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Localization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells. / Wang, Guangli; Zeng, Yao; Chen, Shaoying; Li, Deling; Li, Wei; Zhou, Yanchun; Singer, Robert H.; Gu, Wei.

In: Scientific Reports, Vol. 7, No. 1, 13575, 01.12.2017.

Research output: Contribution to journalArticle

Wang, Guangli ; Zeng, Yao ; Chen, Shaoying ; Li, Deling ; Li, Wei ; Zhou, Yanchun ; Singer, Robert H. ; Gu, Wei. / Localization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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