| First Author | Lambert J | Year | 2020 |
| Journal | J Cell Sci | Volume | 133 |
| Issue | 7 | PubMed ID | 32269093 |
| Mgi Jnum | J:286843 | Mgi Id | MGI:6404733 |
| Doi | 10.1242/jcs.235762 | Citation | Lambert J, et al. (2020) ADAMTS-1 and syndecan-4 intersect in the regulation of cell migration and angiogenesis. J Cell Sci 133(7):jcs235762 |
| abstractText | 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 alpha5 integrin-containing fibrillar adhesions. However, integrin alpha5 null cells still showed increased migration in response to ADAMTS-1 and syndecan-4 siRNA treatment. Plating of naive 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. |
