| http://purl.uniprot.org/citations/25297632 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25297632 | http://www.w3.org/2000/01/rdf-schema#comment | "Clear cell renal cell carcinomas (RCC) frequently display inactivation of von Hippel-Lindau (VHL) gene leading to increased level of hypoxia-inducible factors (HIF). In this study, we investigated the potential role of HIF2α in regulating RCC susceptibility to natural killer (NK) cell-mediated killing. We demonstrated that the RCC cell line 786-0 with mutated VHL was resistant to NK-mediated lysis as compared with the VHL-corrected cell line (WT7). This resistance was found to require HIF2α stabilization. On the basis of global gene expression profiling and chromatin immunoprecipitation assay, we found ITPR1 (inositol 1,4,5-trisphosphate receptor, type 1) as a direct novel target of HIF2α and that targeting ITPR1 significantly increased susceptibility of 786-0 cells to NK-mediated lysis. Mechanistically, HIF2α in 786-0 cells lead to overexpression of ITPR1, which subsequently regulated the NK-mediated killing through the activation of autophagy in target cells by NK-derived signal. Interestingly, both ITPR1 and Beclin-1 silencing in 786-0 cells inhibited NK-induced autophagy and subsequently increased granzyme B activity in target cells. Finally, in vivo ITPR1 targeting significantly enhanced the NK-mediated tumor regression. Our data provide insight into the link between HIF2α, the ITPR1-related pathway, and natural immunity and strongly suggest a role for the HIF2α/ITPR1 axis in regulating RCC cell survival."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-14-0303"xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Thiery J."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Baud V."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Olive D."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Escudier B."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Janji B."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Gardie B."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Donnadieu E."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Boutet M."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Chouaib S."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Ferlicot S."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Richon C."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Tittarelli A."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Billot K."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Hasmim M."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Messai Y."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Couve S."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Noman M.Z."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Albiges L."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Orlanducci F."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Viry E."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Nanbakhsh A."xsd:string |
| http://purl.uniprot.org/citations/25297632 | http://purl.uniprot.org/core/author | "Ben Safta T."xsd:string |