Tumor matrix stiffness promotes metastatic cancer cell interaction with the endothelium
| Autor: | Colin Nixon, Steven Reid, Vasileios Papalazarou, Laura M. Machesky, Ewan J. McGhee, Lisa J. Neilson, David M. Bryant, Ralf H. Adams, Francesca Patella, Karthic Swaminathan, Sandeep Dhayade, Jens Serneels, Karen Blyth, Álvaro Román-Fernández, Shehab Ismail, Manuel Salmerón-Sánchez, Alice Santi, Massimiliano Mazzone, Sara Zanivan, Yasmin ElMaghloob, Emily J. Kay, Juan Ramon Hernandez-Fernaud, Leo M. Carlin, Dimitris Athineos, Anne Theres Henze, John B. G. Mackey |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CCN1/CYR61 Endothelium Cell Communication Biology Article Mass Spectrometry General Biochemistry Genetics and Molecular Biology Cell Line Metastasis blood vessels Extracellular matrix stiffness 03 medical and health sciences proteomics cancer metastasis medicine Humans Molecular Biology beta Catenin Cancer General Immunology and Microbiology General Neuroscience Matricellular protein Endothelial Cells Articles Cadherins medicine.disease 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Tumor progression CYR61 Cancer cell Immunology Cancer research Melanocytes Cell Adhesion Polarity & Cytoskeleton Cysteine-Rich Protein 61 |
| Zdroj: | The EMBO Journal |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.15252/embj.201694912 |
| Popis: | 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. ispartof: EMBO Journal vol:36 issue:16 pages:2373-2389 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text