文章基本信息

标题：Localization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells
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作者：Guangli Wang ; Yao Zeng ; Shaoying Chen 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2017
卷号：7
期号：1
DOI：10.1038/s41598-017-14148-8
语种：English
出版社：Springer Nature
摘要：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.