ADAMTS-1 and Syndecan-4 intersect in the regulation of cell migration and angiogenesis

Lambert, Jordi, Makin, Kate, Akbareian, Sophia, Johnson, Robert, Alghamdi, Abdullah, Robinson, Stephen ORCID: and Edwards, Dylan ORCID: (2020) ADAMTS-1 and Syndecan-4 intersect in the regulation of cell migration and angiogenesis. Journal of Cell Science, 133 (7). ISSN 0021-9533

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ADAMTS-1 is an extracellular protease with critical roles in organogenesis and angiogenesis. Here we demonstrate a functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan-4 in influencing adhesion, migration and angiogenesis. Knockdown of ADAMTS-1 in endothelial cells resulted in a parallel reduction in cell surface syndecan-4, attributable to increased matrix metalloproteinase-9 (MMP9) activity. Knockdown of either ADAMTS-1 or syndecan-4 increased cellular responses to vascular endothelial growth factor A isoform VEGFA164, and increased ex vivo aortic ring microvessel sprouting. On fibronectin, knockdown of either protein enhanced migration and promoted formation of long α5 integrin-containing fibrillar adhesions. However, integrin α5 null cells still showed increased migration in response to ADAMTS-1 and syndecan-4 siRNA treatment. Plating of naïve endothelial cells on cell-conditioned matrix from ADAMTS-1 and syndecan-4 knockdown cells demonstrated that the altered adhesive behaviour was matrix dependent, and this correlated with a lack of expression of fibulin-1: an extracellular matrix co-factor for ADAMTS-1 that is known to inhibit migration. These findings support the notion that ADAMTS-1 and syndecan-4 are functionally interconnected in regulating cell migration and angiogenesis, via collaboration with MMP9 and fibulin-1.This article has an associated First Person interview with the first author of the paper.

Item Type: Article
Uncontrolled Keywords: adamts,angiogenesis,extracellular matrix,migration,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1307
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Science > School of Biological Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies
Faculty of Science > Research Groups > Cells and Tissues
Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
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Depositing User: LivePure Connector
Date Deposited: 27 Feb 2020 08:28
Last Modified: 19 Jul 2024 22:30
DOI: 10.1242/jcs.235762


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