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

4 Scopus citations

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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