| http://purl.uniprot.org/citations/22363690 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22363690 | http://www.w3.org/2000/01/rdf-schema#comment | "The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation)."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0031624"xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Charpentier B."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Mortier E."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Ferrini S."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Eid P."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Azzi S."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Azzarone B."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Giron-Michel J."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Croce M."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Caignard A."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Chouaib S."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Francois H."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Devocelle A."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Khawam K."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/author | "Lecru L."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/pages | "e31624"xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/title | "Interleukin-15 plays a central role in human kidney physiology and cancer through the gammac signaling pathway."xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://purl.uniprot.org/core/volume | "7"xsd:string |
| http://purl.uniprot.org/citations/22363690 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22363690 |
| http://purl.uniprot.org/citations/22363690 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22363690 |
| http://purl.uniprot.org/uniprot/#_A0A3G1CD75-mappedCitation-22363690 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22363690 |