| http://purl.uniprot.org/citations/31919052 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31919052 | http://www.w3.org/2000/01/rdf-schema#comment | "Glioblastoma (GBM) is a lethal brain tumor containing a subpopulation of glioma stem cells (GSC). Pan-cancer analyses have revealed that stemness of cancer cells correlates positively with immunosuppressive pathways in many solid tumors, including GBM, prompting us to conduct a gain-of-function screen of epigenetic regulators that may influence GSC self-renewal and tumor immunity. The circadian regulator CLOCK emerged as a top hit in enhancing stem-cell self-renewal, which was amplified in about 5% of human GBM cases. CLOCK and its heterodimeric partner BMAL1 enhanced GSC self-renewal and triggered protumor immunity via transcriptional upregulation of OLFML3, a novel chemokine recruiting immune-suppressive microglia into the tumor microenvironment. In GBM models, CLOCK or OLFML3 depletion reduced intratumoral microglia density and extended overall survival. We conclude that the CLOCK-BMAL1 complex contributes to key GBM hallmarks of GSC maintenance and immunosuppression and, together with its downstream target OLFML3, represents new therapeutic targets for this disease. SIGNIFICANCE: Circadian regulator CLOCK drives GSC self-renewal and metabolism and promotes microglia infiltration through direct regulation of a novel microglia-attracting chemokine, OLFML3. CLOCK and/or OLFML3 may represent novel therapeutic targets for GBM.This article is highlighted in the In This Issue feature, p. 327."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.org/dc/terms/identifier | "doi:10.1158/2159-8290.cd-19-0400"xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Chen P."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Zhou A."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Hsu W.H."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Chang A."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "DePinho R.A."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Lan Z."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Tan Z."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Lang F.F."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Spring D.J."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/author | "Wang Y.A."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/name | "Cancer Discov"xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/pages | "371-381"xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/title | "Circadian Regulator CLOCK Recruits Immune-Suppressive Microglia into the GBM Tumor Microenvironment."xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/31919052 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31919052 |
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