| http://purl.uniprot.org/citations/20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20961996 | http://www.w3.org/2000/01/rdf-schema#comment | "In human neuroblastoma, amplification of the MYCN gene predicts poor prognosis and resistance to therapy. Because hypoxia contributes to aggressive tumor phenotypes, predominantly via two structurally related hypoxia inducible factors, HIF-1α and HIF-2α, we examined hypoxia responses in MYCN-amplified neuroblastoma cells. We demonstrate here that HIF-1α, but not HIF-2α, is preferentially expressed in both MYCN-amplified neuroblastoma cells and primary tumors in comparison to samples without MYCN amplification. Our results showed that interplay between N-Myc and HIF-1α plays critical roles in neuroblastoma. For example, high levels of N-Myc override HIF-1α inhibition of cell cycle progression, enabling continued proliferation under hypoxia. Furthermore, both HIF-1α and N-Myc are essential for the Warburg effect (aerobic glycolysis) in neuroblastomas by activating the transcription of multiple glycolytic genes. Of note, expressions of Phosphoglycerate Kinase 1 (PGK1), Hexokinase 2 (HK2), and Lactate Dehydrogenase A (LDHA) were each significantly higher in MYCN-amplified neuroblastomas than in tumors without MYCN amplification. Interestingly, MYCN-amplified neuroblastoma cells are "addicted" to LDHA enzymatic activity, as its depletion completely inhibits tumorigenesis in vivo. Thus, our results provide mechanistic insights explaining how MYCN-amplified neuroblastoma cells contend with hypoxic stress and paradoxically how hypoxia contributes to neuroblastoma aggressiveness through combinatorial effects of N-Myc and HIF-1α. These results also suggest that LDHA represents a novel, pharmacologically tractable target for neuroblastoma therapeutics."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-10-0740"xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/author | "Martinez D."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/author | "Simon M.C."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/author | "Maris J.M."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/author | "Qing G."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/author | "Pawel B."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/author | "Skuli N."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/author | "Mayes P.A."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/pages | "10351-10361"xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/title | "Combinatorial regulation of neuroblastoma tumor progression by N-Myc and hypoxia inducible factor HIF-1alpha."xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://purl.uniprot.org/core/volume | "70"xsd:string |
| http://purl.uniprot.org/citations/20961996 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/20961996 |
| http://purl.uniprot.org/citations/20961996 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/20961996 |
| http://purl.uniprot.org/uniprot/#_A0A166VE84-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |
| http://purl.uniprot.org/uniprot/#_A0A1W2PPD9-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |
| http://purl.uniprot.org/uniprot/#_B4DRZ1-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |
| http://purl.uniprot.org/uniprot/#_B4DP83-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |
| http://purl.uniprot.org/uniprot/#_P04198-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |
| http://purl.uniprot.org/uniprot/#_Q7Z7Q9-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |
| http://purl.uniprot.org/uniprot/#_Q9UMQ5-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |
| http://purl.uniprot.org/uniprot/#_Q9H224-mappedCitation-20961996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/20961996 |