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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.
dc.identifier.urihttp://hdl.handle.net/10454/17727
dc.descriptionYes
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.
dc.description.sponsorshipCancer Research UK (CRUK Beatson Institute C596/A17196, CRUK Glasgow Centre C596/A18076 and S.Z. C596/A12935)
dc.language.isoen
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/)
dc.subjectCCN1/CYR61
dc.subjectBlood vessels
dc.subjectCancer metastatis
dc.subjectProteomics
dc.subjectStiffness
dc.titleTumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium
dc.status.refereedYes
dc.date.Accepted2017-06-09
dc.date.application2017-07-10
dc.typeArticle
dc.type.versionPublished version
dc.identifier.doihttps://doi.org/10.15252/embj.201694912
dc.rights.licenseCC-BY
dc.date.updated2020-03-16T10:10:00Z
refterms.dateFOA2020-03-16T10:19:54Z
dc.openaccess.statusopenAccess


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