Matches in SemOpenAlex for { <https://semopenalex.org/work/W4282938368> ?p ?o ?g. }
Showing items 1 to 68 of
68
with 100 items per page.
- W4282938368 endingPage "1165" @default.
- W4282938368 startingPage "1165" @default.
- W4282938368 abstract "Abstract The Nuclear receptor Glucocorticoid receptor (GR) acts as a ubiquitous hormone-dependent transcription factor, which regulates many cellular functions. Here, we discovered that some ETS (E-twenty-six) family transcription factors form physical complexes with GR. Two members of the family, FLI1 and ERG exhibited stronger binding with the ligand-activated GR. GR-FLI1 interaction enhance the transcriptional activity of DNA-bound GR. Antagonizing GR or lowering cortisol levels in Ewing sarcoma (ES) animal models, a pediatric bone malignancy driven by EWS-FLI1 fusion, robustly retarded tumor growth, as well as inhibited bone to lung metastasis. These findings prompted us to identify prognostic, GR-regulated gene signature in ES. Because the genomic binding sites of GR in ES are still unknown, using chromatin immunoprecipitation followed by high-throughput DNA sequencing in A673 cells we found previously known and new target genes of GR. By utilizing the protein-fragment complementation assay (PCA), we discovered that GR physically interacts with additional ETS factors. Disruption of this complex is enabled by clinically approved GR antagonist RU486 or newly developed selective GR modulators (i.e., SGRMs without AR or PR cross-reactivity). ETS proteins has been strongly associated with tumor progression and metastasis in several cancers. Taken together, we hypothesised that these mechanisms are also relevant for other ETS rearranged cancers. Results of co-immunoprecipitation analysis confirm the interaction of GR and ERG/ETV4 in ETS-positive prostate cancer cells. In addition, migration and proliferation were reduced when we knocked-down or antagonized GR. It is important noting that the pharmacology of GR is very well developed and some GR-targeting drugs are among the most prescribed medicines. These discoveries will open the way to clinical tests and eventual application of anti- hormone therapy in the discipline of pediatric sarcomas and ETS-rearranged cancers. Citation Format: Arunachalam Sekar, Nishanth Belugali Nataraj, Yosef Yarden. Therapeutic targeting of glucocorticoid receptor in ETS rearranged cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1165." @default.
- W4282938368 created "2022-06-16" @default.
- W4282938368 creator A5064201892 @default.
- W4282938368 creator A5084328988 @default.
- W4282938368 date "2022-06-15" @default.
- W4282938368 modified "2023-10-07" @default.
- W4282938368 title "Abstract 1165: Therapeutic targeting of glucocorticoid receptor in ETS rearranged cancer" @default.
- W4282938368 doi "https://doi.org/10.1158/1538-7445.am2022-1165" @default.
- W4282938368 hasPublicationYear "2022" @default.
- W4282938368 type Work @default.
- W4282938368 citedByCount "0" @default.
- W4282938368 crossrefType "journal-article" @default.
- W4282938368 hasAuthorship W4282938368A5064201892 @default.
- W4282938368 hasAuthorship W4282938368A5084328988 @default.
- W4282938368 hasConcept C101762097 @default.
- W4282938368 hasConcept C104317684 @default.
- W4282938368 hasConcept C111829193 @default.
- W4282938368 hasConcept C121608353 @default.
- W4282938368 hasConcept C134320426 @default.
- W4282938368 hasConcept C150194340 @default.
- W4282938368 hasConcept C153911025 @default.
- W4282938368 hasConcept C2777937962 @default.
- W4282938368 hasConcept C2779013556 @default.
- W4282938368 hasConcept C2780192828 @default.
- W4282938368 hasConcept C2993561819 @default.
- W4282938368 hasConcept C502942594 @default.
- W4282938368 hasConcept C54355233 @default.
- W4282938368 hasConcept C59493245 @default.
- W4282938368 hasConcept C81350143 @default.
- W4282938368 hasConcept C86339819 @default.
- W4282938368 hasConcept C86803240 @default.
- W4282938368 hasConceptScore W4282938368C101762097 @default.
- W4282938368 hasConceptScore W4282938368C104317684 @default.
- W4282938368 hasConceptScore W4282938368C111829193 @default.
- W4282938368 hasConceptScore W4282938368C121608353 @default.
- W4282938368 hasConceptScore W4282938368C134320426 @default.
- W4282938368 hasConceptScore W4282938368C150194340 @default.
- W4282938368 hasConceptScore W4282938368C153911025 @default.
- W4282938368 hasConceptScore W4282938368C2777937962 @default.
- W4282938368 hasConceptScore W4282938368C2779013556 @default.
- W4282938368 hasConceptScore W4282938368C2780192828 @default.
- W4282938368 hasConceptScore W4282938368C2993561819 @default.
- W4282938368 hasConceptScore W4282938368C502942594 @default.
- W4282938368 hasConceptScore W4282938368C54355233 @default.
- W4282938368 hasConceptScore W4282938368C59493245 @default.
- W4282938368 hasConceptScore W4282938368C81350143 @default.
- W4282938368 hasConceptScore W4282938368C86339819 @default.
- W4282938368 hasConceptScore W4282938368C86803240 @default.
- W4282938368 hasIssue "12_Supplement" @default.
- W4282938368 hasLocation W42829383681 @default.
- W4282938368 hasOpenAccess W4282938368 @default.
- W4282938368 hasPrimaryLocation W42829383681 @default.
- W4282938368 hasRelatedWork W1207772460 @default.
- W4282938368 hasRelatedWork W1843078452 @default.
- W4282938368 hasRelatedWork W1997130480 @default.
- W4282938368 hasRelatedWork W2088245805 @default.
- W4282938368 hasRelatedWork W2089087147 @default.
- W4282938368 hasRelatedWork W2775736814 @default.
- W4282938368 hasRelatedWork W2897422513 @default.
- W4282938368 hasRelatedWork W3047053717 @default.
- W4282938368 hasRelatedWork W3215568609 @default.
- W4282938368 hasRelatedWork W83261268 @default.
- W4282938368 hasVolume "82" @default.
- W4282938368 isParatext "false" @default.
- W4282938368 isRetracted "false" @default.
- W4282938368 workType "article" @default.