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dc.contributor.authorReid, SE
dc.contributor.authorKay, EJ
dc.contributor.authorNeilson, LJ
dc.contributor.authorHenze, AT
dc.contributor.authorSerneels, J
dc.contributor.authorMcGhee, EJ
dc.contributor.authorDhayade, S
dc.contributor.authorNixon, C
dc.contributor.authorMackey, JB
dc.contributor.authorSanti, A
dc.contributor.authorSwaminathan, Karthic
dc.contributor.authorAthineos, D
dc.contributor.authorPapalazarou, V
dc.contributor.authorPatella, F
dc.contributor.authorRoman-Fernandez, A
dc.contributor.authorElMaghloob, Y
dc.contributor.authorHernandez-Fernaud, JR
dc.contributor.authorAdams, RH
dc.contributor.authorIsmail, S
dc.contributor.authorBryant, DM
dc.contributor.authorSalmeron-Sanchez, M
dc.contributor.authorMachesky, LM
dc.contributor.authorCarlin, LM
dc.contributor.authorBlyth, K
dc.contributor.authorMazzone, M
dc.contributor.authorZanivan, S
dc.date.accessioned2020-03-16T10:09:52Z
dc.date.accessioned2020-03-16T10:17:56Z
dc.date.available2020-03-16T10:09:52Z
dc.date.available2020-03-16T10:17:56Z
dc.date.issued2017-08-15
dc.identifier.citationReid SE, Kay EJ, Neilson LJ et al (2017) Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium. EMBO Journal. 36(16): 2373-2389.en_US
dc.identifier.urihttp://hdl.handle.net/10454/17727
dc.descriptionYesen_US
dc.description.abstractTumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis.en_US
dc.description.sponsorshipCancer Research UK (CRUK Beatson Institute C596/A17196, CRUK Glasgow Centre C596/A18076 and S.Z. C596/A12935)en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.15252/embj.201694912en_US
dc.rights(c) 2017 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license (https://creativecommons.org/licenses/by/4.0/)en_US
dc.subjectCCN1/CYR61en_US
dc.subjectBlood vesselsen_US
dc.subjectCancer metastatisen_US
dc.subjectProteomicsen_US
dc.subjectStiffnessen_US
dc.titleTumor matrix stiffness promotes metastatic cancer cell interaction with the endotheliumen_US
dc.status.refereedYesen_US
dc.date.Accepted2017-06-09
dc.date.application2017-07-10
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.date.updated2020-03-16T10:10:00Z
refterms.dateFOA2020-03-16T10:19:54Z


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