| http://purl.uniprot.org/citations/25082812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25082812 | http://www.w3.org/2000/01/rdf-schema#comment | "Nonsteroidal anti-inflammatory drugs such as sulindac inhibit Wnt signaling, which is critical to maintain cancer stem cell-like cells (CSC), but they also suppress the activity of 5-lipoxygenase (5-LO) at clinically feasible concentrations. Recently, 5-LO was shown to be critical to maintain CSC in a model of chronic myeloid leukemia. For these reasons, we hypothesized that 5-LO may offer a therapeutic target to improve the management of acute myeloid leukemia (AML), an aggressive disease driven by CSCs. Pharmacologic and genetic approaches were used to evaluate the effects of 5-LO blockade in a PML/RARα-positive model of AML. As CSC models, we used Sca-1(+)/lin(-) murine hematopoietic stem and progenitor cells (HSPC), which were retrovirally transduced with PML/RARα. We found that pharmacologic inhibition of 5-LO interfered strongly with the aberrant stem cell capacity of PML/RARα-expressing HSPCs. Through small-molecule inhibitor studies and genetic disruption of 5-LO, we also found that Wnt and CSC inhibition is mediated by the enzymatically inactive form of 5-LO, which hinders nuclear translocation of β-catenin. Overall, our findings revealed that 5-LO inhibitors also inhibit Wnt signaling, not due to the interruption of 5-LO-mediated lipid signaling but rather due to the generation of a catalytically inactive form of 5-LO, which assumes a new function. Given the evidence that CSCs mediate AML relapse after remission, eradication of CSCs in this setting by 5-LO inhibition may offer a new clinical approach for immediate evaluation in patients with AML. Cancer Res; 74(18); 5244-55. ©2014 AACR."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-13-3012"xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Roos J."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Fleming I."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Proschak E."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Held H."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Steinhilber D."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Khan D."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Ruthardt M."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Puccetti E."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Maier T.J."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Oancea C."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Capelo R."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Heinssmann M."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "Kahnt A.S."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/author | "la Buscato E."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/pages | "5244-5255"xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/title | "5-Lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia."xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://purl.uniprot.org/core/volume | "74"xsd:string |
| http://purl.uniprot.org/citations/25082812 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25082812 |
| http://purl.uniprot.org/citations/25082812 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25082812 |
| http://purl.uniprot.org/uniprot/#_E9QA93-mappedCitation-25082812 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25082812 |