http://purl.uniprot.org/citations/20959490 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/20959490 | http://www.w3.org/2000/01/rdf-schema#comment | "Signal transducers and activators of transcription 3 (Stat3) is activated by cytokines and growth factors in lung cancers and regulates expression of genes implicated in cell growth, survival, and transformation. Previously, we found that mice with a deletion of the G protein-coupled receptor, family C, group 5, member a (Gprc5a) gene develop lung tumors, indicating that Gprc5a is a tumor suppressor. Herein, we show that epithelial cells from Gprc5a knockout mouse lung (Gprc5a(-/-) cells) survive better in vitro in medium deprived of exogenous growth factors and form more colonies in semisolid medium than their counterparts from wild-type mice (Gprc5a(+/+) cells). Stat3 tyrosine 705 phosphorylation and expression of several Stat3-regulated antiapoptotic genes were higher in Gprc5a(-/-) than in Gprc5a(+/+) cells. Both cell types secreted leukemia inhibitory factor (Lif); however, whereas Stat3 activation was persistent in Gprc5a(-/-) cells, it was transient in Gprc5a(+/+) cells. Lung adenocarcinoma cells isolated from Gprc5a(-/-) mice also exhibited autocrine Lif-mediated Stat3 activation. The level of Socs3, the endogenous Stat3 inhibitory protein, was higher in Gprc5a(+/+) than in Gprc5a(-/-) cells, and expression of the tumor suppressor stabilized Socs3. Inhibition of Stat3 signaling in Gprc5a(-/-) normal and cancer cells by the Janus-activated kinase 2 inhibitor AG490 or by a dominant negative Stat3(Y705F) increased starvation-induced apoptosis and inhibited colony formation. These results show that persistent Stat3 activation is important for the survival and transformation of Gprc5a(-/-) lung cells and suggest that the tumor suppressive effects of Gprc5a are mediated, at least in part, by inhibition of Stat3 signaling through Socs3 stabilization."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-10-0518"xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/author | "Deng J."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/author | "Fujimoto J."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/author | "Lotan R."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/author | "Men T."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/author | "Lotan D."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/author | "Kadara H."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/pages | "8917-8926"xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/title | "Gprc5a deletion enhances the transformed phenotype in normal and malignant lung epithelial cells by eliciting persistent Stat3 signaling induced by autocrine leukemia inhibitory factor."xsd:string |
http://purl.uniprot.org/citations/20959490 | http://purl.uniprot.org/core/volume | "70"xsd:string |
http://purl.uniprot.org/citations/20959490 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20959490 |
http://purl.uniprot.org/citations/20959490 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20959490 |
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http://purl.uniprot.org/uniprot/#_P42227-mappedCitation-20959490 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20959490 |
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http://purl.uniprot.org/uniprot/P42227 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/20959490 |