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dc.contributor.authorBudden, Timothy
dc.contributor.authorGaudy-Marqueste, Caroline
dc.contributor.authorPorter, Andrew; orcid: 0000-0002-3353-7002
dc.contributor.authorKay, Emily
dc.contributor.authorGurung, Shilpa
dc.contributor.authorEarnshaw, Charles H; orcid: 0000-0002-7926-8506
dc.contributor.authorRoeck, Katharina
dc.contributor.authorCraig, Sarah; orcid: 0000-0003-1928-582X
dc.contributor.authorTraves, Víctor
dc.contributor.authorKrutmann, Jean; orcid: 0000-0001-8433-1517
dc.contributor.authorMuller, Patricia
dc.contributor.authorMotta, Luisa
dc.contributor.authorZanivan, Sara; orcid: 0000-0002-9880-9099
dc.contributor.authorMalliri, Angeliki; orcid: 0000-0001-6848-090X
dc.contributor.authorFurney, Simon J; orcid: 0000-0002-8920-6800
dc.contributor.authorNagore, Eduardo; orcid: 0000-0003-3433-8707
dc.contributor.authorVirós, Amaya; orcid: 0000-0001-5177-5015; email: Amaya.viros@cruk.manchester.ac.uk
dc.date.accessioned2021-06-14T00:53:11Z
dc.date.available2021-06-14T00:53:11Z
dc.date.issued2021-05-12
dc.identifierhttps://chesterrep.openrepository.com/bitstream/handle/10034/624931/article.pdf?sequence=2
dc.identifier.citationNature communications, volume 12, issue 1, page 2742
dc.identifier.urihttp://hdl.handle.net/10034/624931
dc.descriptionFrom Europe PMC via Jisc Publications Router
dc.descriptionHistory: ppub 2021-05-01, epub 2021-05-12
dc.descriptionPublication status: Published
dc.descriptionFunder: Wellcome Trust; Grant(s): 110078/Z/15/Z
dc.descriptionFunder: Cancer Research UK; Grant(s): A27412
dc.description.abstractUltraviolet radiation (UVR) damages the dermis and fibroblasts; and increases melanoma incidence. Fibroblasts and their matrix contribute to cancer, so we studied how UVR modifies dermal fibroblast function, the extracellular matrix (ECM) and melanoma invasion. We confirmed UVR-damaged fibroblasts persistently upregulate collagen-cleaving matrix metalloprotein-1 (MMP1) expression, reducing local collagen (COL1A1), and COL1A1 degradation by MMP1 decreased melanoma invasion. Conversely, inhibiting ECM degradation and MMP1 expression restored melanoma invasion. Primary cutaneous melanomas of aged humans show more cancer cells invade as single cells at the invasive front of melanomas expressing and depositing more collagen, and collagen and single melanoma cell invasion are robust predictors of poor melanoma-specific survival. Thus, primary melanomas arising over collagen-degraded skin are less invasive, and reduced invasion improves survival. However, melanoma-associated fibroblasts can restore invasion by increasing collagen synthesis. Finally, high COL1A1 gene expression is a biomarker of poor outcome across a range of primary cancers.
dc.languageeng
dc.rightsLicence for this article: cc by
dc.sourceissn: 2041-1723
dc.sourceessn: 2041-1723
dc.sourcenlmid: 101528555
dc.subjectFibroblasts
dc.subjectHumans
dc.subjectLentivirus
dc.subjectMelanoma
dc.subjectCollagen
dc.subjectCollagen Type I
dc.subjectMicroscopy, Atomic Force
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectUltraviolet Rays
dc.subjectMass Spectrometry
dc.subjectMatrix Metalloproteinase 1
dc.titleUltraviolet light-induced collagen degradation inhibits melanoma invasion.
dc.typearticle
dc.date.updated2021-06-14T00:53:11Z


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