期刊
FEBS LETTERS
卷 585, 期 20, 页码 3328-3336出版社
WILEY
DOI: 10.1016/j.febslet.2011.09.023
关键词
Breast cancer; Thioredoxin; Matrix metalloproteinase-9; MMP-9/TIMP-1 equilibrium; NF-kappa B; Invasion
资金
- AIRC
- PRIN-Cofin
- Maugeri Foundation
Increased expression of thioredoxin (Trx)-1 and matrix metalloproteinase (MMP)-9 associates with malignant breast cancer progression. Here, we describe a functional relationship between Trx-1 and MMP-9 in promoting MDA-MB-231 breast cancer cell invasive behaviour. Trx-1 overexpression stimulated MMP-9 expression, de-regulated the MMP-9/TIMP-1 equilibrium and augmented MMP-9 involvement in a more invasive phenotype. Trx-1 augmented MMP-9 transcription through NF-kappa B, AP-1 and SP1 elements; stimulated p50/p65 NF-kappa B activity and recruitment to the MMP-9 promoter; and facilitated MMP-9 promoter-accessibility to NF-kappa B by preventing HDAC recruitment and maintaining MMP-9 promoter histone acetylation. Our data provide a functional basis for Trx-1 and MMP-9 association in malignant breast cancer and identify Trx-1 and NF-kappa B as potentially druggable targets for reducing MMP-9 involvement in malignant behaviour. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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