| http://purl.uniprot.org/citations/28481870 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28481870 | http://www.w3.org/2000/01/rdf-schema#comment | "TGF-β is a multifunctional cytokine affecting many cell types and implicated in tissue remodeling processes. Due to its many functions and cell-specific effects, the consequences of TGF-β signaling are process-and stage-dependent, and it is not uncommon that TGF-β exerts distinct and sometimes opposing effects on a disease progression depending on the stage and on the pathological changes associated with the stage. The mechanisms underlying cell- and process-specific effects of TGF-β are poorly understood. We are describing a novel pathway that mediates induction of angiogenesis in response to TGF-β1. We found that in endothelial cells (EC) thrombospondin-4 (TSP-4), a secreted extracellular matrix (ECM) protein, is upregulated in response to TGF-β1 and mediates the effects of TGF-β1 on angiogenesis. Upregulation of TSP-4 does not require the synthesis of new protein, is not caused by decreased secretion of TSP-4, and is mediated by activation of SMAD3. Using Thbs4-/- mice and TSP-4 shRNA, we found that TSP-4 mediated pro-angiogenic functions in cultured EC and angiogenesis in vivo in response to TGF-β1. We observed~3-fold increases in tumor mass and levels of angiogenesis markers in animals injected with TGF-β1, and these effects did not occur in Thbs4-/- animals. Injections of an inhibitor of TGF-β1 signaling SB-431542 also decreased the weights of tumors and cancer angiogenesis. Our results from in vivo angiogenesis models and cultured EC document that TSP-4 mediates upregulation of angiogenesis by TGF-β1. Upregulation of pro-angiogenic TSP-4 and selective effects of TSP-4 on EC may contribute to stimulation of tumor growth by TGF-β despite the inhibition of cancer cell proliferation."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2017.140"xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Xiao R."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Habib N."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Plow E."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Muppala S."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Raman P."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Krukovets I."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Stenina-Adognravi O."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Verbovetsky D."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/author | "Yendamuri R."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/pages | "5189-5198"xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/title | "Thrombospondin-4 mediates TGF-beta-induced angiogenesis."xsd:string |
| http://purl.uniprot.org/citations/28481870 | http://purl.uniprot.org/core/volume | "36"xsd:string |
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