Steven E Reid, Emily J Kay, Lisa J Neilson, Anne-Theres Henze, Jens Serneels, Ewan J McGhee, Sandeep Dhayade, Colin Nixon, John Bg Mackey, Alice Santi, Karthic Swaminathan, Dimitris Athineos, Vasileios Papalazarou, Francesca Patella, Álvaro Román-Fernández, Yasmin ElMaghloob, Juan Ramon Hernandez-Fernaud, Ralf H Adams, Shehab Ismail, David M Bryant, Manuel Salmeron-Sanchez, Laura M Machesky, Leo M Carlin, Karen Blyth, Massimiliano Mazzone, Sara Zanivan
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...
August 15, 2017: EMBO Journal