| Title: |
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: |
urn:ISSN:2045-2322 ; Scientific Reports, 7, 1, 8526 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2017 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
3101 Biochemistry and Cell Biology; 31 Biological Sciences; Cancer; Genetics; 2.1 Biological and endogenous factors; 1.1 Normal biological development and functioning; Binding Sites; Cell Line; Tumor; Gene Expression Regulation; Humans; Interleukin-6; Matrix Metalloproteinase 1; Matrix Metalloproteinase 3; Promoter Regions; Genetic; Protein Binding; Regulatory Elements; Transcriptional; STAT1 Transcription Factor; anzsrc-for: 3101 Biochemistry and Cell Biology; anzsrc-for: 31 Biological Sciences |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/unsworks_53158 |
| DOI: |
10.1038/s41598-017-08581-y |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_53158; https://doi.org/10.1038/s41598-017-08581-y |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.6EB359C2 |
| Database: |
BASE |