Thioredoxin stimulates MMP-9 expression, de-regulates the MMP-9/TIMP-1 equilibrium and promotes MMP-9 dependent invasion in human MDA-MB-231 breast cancer cells

Antonietta R. Farina, Lucia Cappabianca, Giuseppina Desantis, Natalia Di Ianni, Pierdomenico Ruggeri, Marzia Ragone, Stefania Merolle, Kathryn F. Tonissen, Alberto Gulino, Andrew R. MacKay

Research output: Contribution to journalArticle

Abstract

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-κB, AP-1 and SP1 elements; stimulated p50/p65 NF-κB activity and recruitment to the MMP-9 promoter; and facilitated MMP-9 promoter-accessibility to NF-κB 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-κB as potentially druggable targets for reducing MMP-9 involvement in malignant behaviour.

Original languageEnglish
Pages (from-to)3328-3336
Number of pages9
JournalFEBS Letters
Volume585
Issue number20
DOIs
Publication statusPublished - Oct 20 2011

Keywords

  • Breast cancer
  • Invasion
  • Matrix metalloproteinase-9
  • MMP-9/TIMP-1 equilibrium
  • NF-κB
  • Thioredoxin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

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    Farina, A. R., Cappabianca, L., Desantis, G., Ianni, N. D., Ruggeri, P., Ragone, M., Merolle, S., Tonissen, K. F., Gulino, A., & MacKay, A. R. (2011). Thioredoxin stimulates MMP-9 expression, de-regulates the MMP-9/TIMP-1 equilibrium and promotes MMP-9 dependent invasion in human MDA-MB-231 breast cancer cells. FEBS Letters, 585(20), 3328-3336. https://doi.org/10.1016/j.febslet.2011.09.023