| pubmed-article:21102457 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C0027651 | lld:lifeskim |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C1367307 | lld:lifeskim |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C1414253 | lld:lifeskim |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C0205322 | lld:lifeskim |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:21102457 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:21102457 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:21102457 | pubmed:dateCreated | 2010-12-7 | lld:pubmed |
| pubmed-article:21102457 | pubmed:abstractText | Interleukin-6 (IL-6)-Janus kinase (JAK) signaling is viewed as crucial for persistent signal transducer and activator of transcription-3 (STAT3) activation in cancer. However, IL-6-induced STAT3 activation is normally transient. Here we identify a key mechanism for persistent STAT3 activation in tumor cells and the tumor microenvironment. We show that expression of sphingosine-1-phosphate receptor-1 (S1PR1), a G protein-coupled receptor for the lysophospholipid sphingosine-1-phosphate (S1P), is elevated in STAT3-positive tumors. STAT3 is a transcription factor for the S1pr1 gene. Reciprocally, enhanced S1pr1 expression activates STAT3 and upregulates Il6 gene expression, thereby accelerating tumor growth and metastasis in a STAT3-dependent manner. Silencing S1pr1 in tumor cells or immune cells inhibits tumor STAT3 activity, tumor growth and metastasis. S1P-S1PR1-induced STAT3 activation is persistent, in contrast to transient STAT3 activation by IL-6. S1PR1 activates STAT3 in part by upregulating JAK2 tyrosine kinase activity. We show that STAT3-induced S1PR1 expression, as well as the S1P-S1PR1 pathway reciprocal regulation of STAT3 activity, is a major positive feedback loop for persistent STAT3 activation in cancer cells and the tumor microenvironment and for malignant progression. | lld:pubmed |
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| pubmed-article:21102457 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21102457 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21102457 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21102457 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21102457 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21102457 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21102457 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:21102457 | pubmed:issn | 1546-170X | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:GilBB | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:LiuYongY | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:JoveRichardR | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:HerrmannAndre... | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:FormanStephen... | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:SomloGeorgeG | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:YangChunmeiC | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:KujawskiMacie... | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:LeeHeehyoungH | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:KortylewskiMa... | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:HorneDavidD | lld:pubmed |
| pubmed-article:21102457 | pubmed:author | pubmed-author:DengJiehuiJ | lld:pubmed |
| pubmed-article:21102457 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21102457 | pubmed:volume | 16 | lld:pubmed |
| pubmed-article:21102457 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21102457 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21102457 | pubmed:pagination | 1421-8 | lld:pubmed |
| pubmed-article:21102457 | pubmed:dateRevised | 2011-7-28 | lld:pubmed |
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