| http://purl.uniprot.org/citations/16648553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16648553 | http://www.w3.org/2000/01/rdf-schema#comment | "The endothelin-1 (ET-1) axis represents a novel target in several malignancies, including ovarian carcinoma. Upon being activated, the endothelin A receptor (ET(A)R) mediates multiple tumor-promoting activities, including mitogenesis, escape from apoptosis, angiogenesis, metastasis-related protease activation, epithelial-mesenchymal transition, and invasion. Integrin-linked kinase (ILK) is a multidomain focal adhesion protein that conveys intracellular signaling elicited by beta1-integrin and growth factor receptors. In this study, we investigate whether the signaling triggered by ET(A)R leading to an aggressive phenotype is mediated by an ILK-dependent mechanism. In HEY and OVCA 433 ovarian carcinoma cell lines, activation of ET(A)R by ET-1 enhances the expression of alpha2beta1 and alpha3beta1 integrins. ILK activity increases as ovarian cancer cells adhere to type I collagen through beta1 integrin signaling, and do so to a greater extent on ET-1 stimulation. ET-1 increases ILK mRNA and protein expression and activity in a time- and concentration-dependent manner. An ILK small-molecule inhibitor (KP-392) or transfection with a dominant-negative ILK mutant effectively blocks the phosphorylation of downstream signals, Akt and glycogen synthase kinase-3beta. The blockade of ET-1/ET(A)R-induced ILK activity results in an inhibition of matrix metalloproteinase activation as well as of cell motility and invasiveness in a phosphoinositide 3 kinase-dependent manner. In ovarian carcinoma xenografts, ABT-627, a specific ET(A)R antagonist, suppresses ILK expression, Akt and glycogen synthase kinase-3beta phosphorylation, and tumor growth. These data show that ILK functions as a downstream mediator of the ET-1/ET(A)R axis to potentiate aggressive cellular behavior. Thus, the ILK-related signaling cascade can be efficiently targeted by pharmacologic blockade of ET(A)R."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.org/dc/terms/identifier | "doi:10.1158/1535-7163.mct-05-0523"xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/author | "Dedhar S."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/author | "Spinella F."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/author | "Natali P.G."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/author | "Nicotra M.R."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/author | "Bagnato A."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/author | "Di Castro V."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/author | "Rosano L."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/name | "Mol Cancer Ther"xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/pages | "833-842"xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/title | "Integrin-linked kinase functions as a downstream mediator of endothelin-1 to promote invasive behavior in ovarian carcinoma."xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://purl.uniprot.org/core/volume | "5"xsd:string |
| http://purl.uniprot.org/citations/16648553 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16648553 |
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