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Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3.

Authors :
Cutler SJ
Doecke JD
Ghazawi I
Yang J
Griffiths LR
Spring KJ
Ralph SJ
Mellick AS
Source :
Scientific reports [Sci Rep] 2017 Aug 17; Vol. 7 (1), pp. 8526. Date of Electronic Publication: 2017 Aug 17.
Publication Year :
2017

Abstract

Dynamic remodelling of the extracellular matrix (ECM) is a key feature of cancer progression. Enzymes that modify the ECM, such as matrix metalloproteinases (MMPs), have long been recognised as important targets of anticancer therapy. Inflammatory cytokines are known to play a key role in regulating protease expression in cancer. Here we describe the identification of gamma-activated site (GAS)-like, signal transducer and activator of transcription (STAT) binding elements (SBEs) within the proximal promoters of the MMP-1 and MMP-3 genes, which in association with AP-1 components (c-Fos or Jun), bind STAT-1 in a homodimer like complex (HDLC). We further demonstrate that MMP expression and binding of this complex to SBEs can either be enhanced by interleukin (IL)-6, or reduced by interferon gamma (IFN-γ), and that IL-6 regulation of MMPs is not STAT-3 dependent. Collectively, this data adds to existing understanding of the mechanism underlying cytokine regulation of MMP expression via STAT-1, and increases our understanding of the links between inflammation and malignancy in colon cancer.

Details

Language :
English
ISSN :
2045-2322
Volume :
7
Issue :
1
Database :
MEDLINE
Journal :
Scientific reports
Publication Type :
Academic Journal
Accession number :
28819304
Full Text :
https://doi.org/10.1038/s41598-017-08581-y