| http://purl.uniprot.org/citations/22891351 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22891351 | http://www.w3.org/2000/01/rdf-schema#comment | "Although tyrosine-phosphorylated or activated STAT3 (pY-STAT3) is a well-described mediator of tumorigenesis, its role in thyroid cancer has not been investigated. We observed that 63 of 110 (57%) human primary papillary thyroid carcinoma (PTC) cases expressed nuclear pY-STAT3 in tumor cells, preferentially in association with the tumor stroma. An inverse relationship between pY-STAT3 expression with tumor size and the presence of distant metastases was observed. Using human thyroid cancer-derived cell lines [harboring rearranged during transfection (RET)/PTC, v-RAF murine sarcoma viral oncogene homolog B (BRAF), or rat sarcoma virus oncogene (RAS) alterations], we determined that IL-6/gp130/JAK signaling is responsible for STAT3 activation. STAT3 knockdown by shRNA in representative thyroid cancer cell lines that express high levels of pY-STAT3 had no effect on in vitro growth. However, xenografted short hairpin STAT3 cells generated larger tumors than control cells. Similarly, STAT3 deficiency in a murine model of BRAFV600E-induced PTC led to thyroid tumors that were more proliferative and larger than those tumors expressing STAT3wt. Genome expression analysis revealed that STAT3 knockdown resulted in the down-regulation of multiple transcripts, including the tumor suppressor insulin-like growth factor binding protein 7. Furthermore, STAT3 knockdown led to an increase in glucose consumption, lactate production, and expression of Hypoxia-inducible factor 1 (HIF1α) target genes, suggesting that STAT3 is a negative regulator of aerobic glycolysis. Our studies show that, in the context of thyroid cancer, STAT3 is paradoxically a negative regulator of tumor growth. These findings suggest that targeting STAT3 in these cancers could enhance tumor size and highlight the complexities of the role of STAT3 in tumorigenesis."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1201232109"xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Daly L."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Soares P."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Sobrinho-Simoes M."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Lima J."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Bromberg J.F."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Almeida A."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Couto J.P."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Maximo V."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Fagin J.A."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Knauf J.A."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/author | "Lyden D."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/pages | "E2361-70"xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/title | "STAT3 negatively regulates thyroid tumorigenesis."xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://purl.uniprot.org/core/volume | "109"xsd:string |
| http://purl.uniprot.org/citations/22891351 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22891351 |
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| http://purl.uniprot.org/uniprot/P42227#attribution-FE5F44A3F62EC496B9D266D9F3204917 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/22891351 |
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