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dc.contributor.authorCutler, Samuel J
dc.contributor.authorDoecke, James D
dc.contributor.authorGhazawi, Ibtisam
dc.contributor.authorYang, Jinbo
dc.contributor.authorGriffiths, Lyn R
dc.contributor.authorSpring, Kevin J
dc.contributor.authorRalph, Stephen J
dc.contributor.authorMellick, Albert S
dc.date.accessioned2017-11-27T01:27:51Z
dc.date.available2017-11-27T01:27:51Z
dc.date.issued2017
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/s41598-017-08581-y
dc.identifier.urihttp://hdl.handle.net/10072/354122
dc.description.abstractDynamic 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.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherNature Publishing Group
dc.relation.ispartofpagefrom8526-1
dc.relation.ispartofpageto8526-12
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume7
dc.subject.fieldofresearchOncology and Carcinogenesis not elsewhere classified
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchOther Physical Sciences
dc.subject.fieldofresearchcode111299
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0299
dc.titleNovel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/.
dc.description.versionPublished
gro.facultyGriffith Health, School of Medical Science
gro.rights.copyright© The Author(s) 2017.This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
gro.hasfulltextFull Text
gro.griffith.authorDoecke, James D.
gro.griffith.authorGhazawi, Ibtisam
gro.griffith.authorMellick, Albert S.
gro.griffith.authorRalph, Stephen J.
gro.griffith.authorCutler, Samuel J.
gro.griffith.authorGriffiths, Lyn
gro.griffith.authorSpring, Kevin


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