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

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 r...

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Autores principales:	Samuel J. Cutler, James D. Doecke, Ibtisam Ghazawi, Jinbo Yang, Lyn R. Griffiths, Kevin J. Spring, Stephen J. Ralph, Albert S. Mellick
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e8b635bf4b804c1283b84d769ec90929
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spelling	oai:doaj.org-article:e8b635bf4b804c1283b84d769ec909292021-12-02T11:41:11ZNovel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-310.1038/s41598-017-08581-y2045-2322https://doaj.org/article/e8b635bf4b804c1283b84d769ec909292017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08581-yhttps://doaj.org/toc/2045-2322Abstract 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.Samuel J. CutlerJames D. DoeckeIbtisam GhazawiJinbo YangLyn R. GriffithsKevin J. SpringStephen J. RalphAlbert S. MellickNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Samuel J. Cutler James D. Doecke Ibtisam Ghazawi Jinbo Yang Lyn R. Griffiths Kevin J. Spring Stephen J. Ralph Albert S. Mellick Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
description	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.
format	article
author	Samuel J. Cutler James D. Doecke Ibtisam Ghazawi Jinbo Yang Lyn R. Griffiths Kevin J. Spring Stephen J. Ralph Albert S. Mellick
author_facet	Samuel J. Cutler James D. Doecke Ibtisam Ghazawi Jinbo Yang Lyn R. Griffiths Kevin J. Spring Stephen J. Ralph Albert S. Mellick
author_sort	Samuel J. Cutler
title	Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
title_short	Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
title_full	Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
title_fullStr	Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
title_full_unstemmed	Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3
title_sort	novel stat binding elements mediate il-6 regulation of mmp-1 and mmp-3
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e8b635bf4b804c1283b84d769ec90929
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Novel STAT binding elements mediate IL-6 regulation of MMP-1 and MMP-3

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