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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
Miyuki Chijiiwa, Satsuki Mochizuki, Tokuhiro Kimura, Hitoshi Abe, Yukie Tanaka, Yutaka Fujii, Hidenori Shimizu, Hiroyuki Enomoto, Yoshiaki Toyama, Yasunori Okada
OBJECTIVE: ADAMTS-4, also called aggrecanase 1, is considered to play a key role in aggrecan degradation in human osteoarthritic (OA) cartilage, but information about regulators of ADAMTS-4 aggrecanase activity remains limited. We undertook this study to search for molecules that modulate ADAMTS-4 activity. METHODS: Molecules copurified with ADAMTS-4 from ADAMTS-4-transfected chondrocytic cells were sequenced by nanoscale liquid chromatography tandem mass spectrometry...
June 2015: Arthritis & Rheumatology
Rabea Hinkel, Teresa Trenkwalder, Björn Petersen, Wira Husada, Florian Gesenhues, Seungmin Lee, Ewald Hannappel, Ildiko Bock-Marquette, Daniel Theisen, Laura Leitner, Peter Boekstegers, Czeslaw Cierniewski, Oliver J Müller, Ferdinand le Noble, Ralf H Adams, Christine Weinl, Alfred Nordheim, Bruno Reichart, Christian Weber, Eric Olson, Guido Posern, Elisabeth Deindl, Heiner Niemann, Christian Kupatt
Gradual occlusion of coronary arteries may result in reversible loss of cardiomyocyte function (hibernating myocardium), which is amenable to therapeutic neovascularization. The role of myocardin-related transcription factors (MRTFs) co-activating serum response factor (SRF) in this process is largely unknown. Here we show that forced MRTF-A expression induces CCN1 and CCN2 to promote capillary proliferation and pericyte recruitment, respectively. We demonstrate that, upon G-actin binding, thymosin ß4 (Tß4), induces MRTF translocation to the nucleus, SRF-activation and CCN1/2 transcription...
June 9, 2014: Nature Communications
Tomasz Andrzej Bonda, Andrzej Taranta, Karol Adam Kaminski, Magdalena Dziemidowicz, Sergey Litvinovich, Marcin Kozuch, Izabela Bialuk, Lech Chyczewski, Maria Malgorzata Winnicka
Chronic heart failure often leads to worsening of the renal function. Mediators of this process include inflammatory and neuroendocrine factors. CCN1 (Cyr 61), a member of growth factor-inducible immediate early genes, which modulates inflammation and fibrogenesis, is excreted with urine in the early phase of acute renal injury and may be involved in the pathogenesis of the cardiorenal syndrome. The aim of the study was to evaluate CCN1 protein abundance and localization in the kidney of IL-6-deficient C57BL/6J (IL-6 KO) mice and respective wild-type (WT) animals in basal conditions and in animals with chronic heart failure twelve weeks after myocardial infarction...
2013: Folia Histochemica et Cytobiologica
Shane E Holloway, Adam W Beck, Luc Girard, M Raffat Jaber, Carlton C Barnett, Rolf A Brekken, Jason B Fleming
BACKGROUND: Identification of extracellular matrix proteins (ECM) associated with tumor cell metastasis may generate targets for future therapy against pancreatic cancer metastases. We hypothesized that comparison of ECM-associated gene expression in primary and metastatic pancreatic tumors would identify ECM proteins associated with pancreatic metastasis. STUDY DESIGN: A clinically relevant model of pancreatic cancer was used to generate RNA from primary and metastatic tumors; it was evaluated by microarray analysis with subsequent cluster analysis...
March 2005: Journal of the American College of Surgeons
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