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Sci Rep. 2017 Oct 19;7(1):13575. doi: 10.1038/s41598-017-14148-8.

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

Author information

1
Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province, 515041, China.
2
Anatomy and Structural Biology, Einstein College of Medicine, Bronx, New York, 10461, USA.
3
Department of Pathophysiology, The Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, Guangdong Province, 515041, China. weigu1@yahoo.com.

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.

PMID:
29051606
PMCID:
PMC5648759
DOI:
10.1038/s41598-017-14148-8
[Indexed for MEDLINE]
Free PMC Article

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