Reid, SE;
Kay, EJ;
Neilson, LJ;
Henze, A-T;
Serneels, J;
McGhee, EJ;
Dhayade, S;
... Zanivan, S; + view all
(2017)
Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium.
The EMBO Journal
, 36
(16)
pp. 2373-2389.
10.15252/embj.201694912.
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Abstract
Tumor 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.
| Type: | Article |
|---|---|
| Title: | Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.15252/embj.201694912 |
| Publisher version: | https://doi.org/10.15252/embj.201694912 |
| Language: | English |
| Additional information: | © 2017 Cancer Research UK Beatson Institute. Published under the terms of the CC BY 4.0 license. |
| Keywords: | CCN1/CYR61; stiffness; blood vessels; proteomics; cancer metastasis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10074409 |
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