biostudies-literatureWang GNIGMS NIH HHS13575https://www.ebi.ac.uk/biostudies/studies/S-EPMC5648759biostudies-literatureUnknown7(1)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-2? attenuated the binding of AP-2? 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.Scientific reportsLocalization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells.PMC5648759R01 GM057071Li WLi DSinger RHGu WWang GZeng YChen SZhou YfalseLocalization of TFPI-2 in the nucleus modulates MMP-2 gene expression in breast cancer cells.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-2? attenuated the binding of AP-2? 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.2017-01-01T00:00:00Z2017 Oct2021-03-14T08:56:57Z2019-03-27T02:59:25ZS-EPMC56487592905160610.1038/s41598-017-14148-8