Matches in SemOpenAlex for { <https://semopenalex.org/work/W1865854714> ?p ?o ?g. }
Showing items 1 to 90 of
90
with 100 items per page.
- W1865854714 abstract "Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAHeat Shock Factor 1 (HSF1) is a key transcription factor involved in proteostasis and response to stress, as well as being implicated in many diseases including cancer. Up-regulation of its activity by environmental stress or oncogenesis leads to transcriptional induction of genes involved in diverse cellular processes supporting the cancer state, including proteostasis, proliferation, survival and metastasis. Inhibition of HSF1 is therefore potentially beneficial for cancer treatment, but HSF1 is not technically druggable. We developed a high-throughput cell-based reporter gene assay to screen a library of small-molecule kinase inhibitors and identified 3 compound series as validated inhibitors of HSF1 activation by the HSP90 inhibitor 17-AAG. Further characterization of imidazo[1,2-b]pyridazine compounds showed inhibition of HSF1 target gene expression and the ability to mimic other features of the HSF1 knockdown phenotype. Using these tool compounds and by siRNA knockdown of HSF1 expression we demonstrate that HSF1 inhibition leads to cell cycle arrest and enhances the antiproliferative effect of 17-AAG. In addition, we show that HSP90 inhibition induces HSF1 phosphorylation at two serine residues, Ser326 and Ser320, highlighting the importance of Ser320 phosphorylation in HSP72 up-regulation by 17-AAG-induced HSF1 activation, and show that this activation is inhibited by our tool compounds. Our findings support the optimization and development of small-molecule inhibitors of the HSF1 pathway for cancer treatment.Note: This abstract was not presented at the meeting.Citation Format: Emmanuel de Billy, Nicola Chessum, Robert Te Poele, Jennifer Smith, Lorenzo Zani, Swee Sharp, Mark Stubbs, Wynne Aherne, Keith Jones, Paul Workman. Identification of small molecule inhibitors of HSF1 stress pathway activation in cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1775. doi:10.1158/1538-7445.AM2014-1775" @default.
- W1865854714 created "2016-06-24" @default.
- W1865854714 creator A5003965204 @default.
- W1865854714 creator A5006946698 @default.
- W1865854714 creator A5034700257 @default.
- W1865854714 creator A5052714030 @default.
- W1865854714 creator A5056212024 @default.
- W1865854714 creator A5058033074 @default.
- W1865854714 creator A5065737376 @default.
- W1865854714 creator A5075096091 @default.
- W1865854714 creator A5075359536 @default.
- W1865854714 creator A5084313119 @default.
- W1865854714 date "2014-09-30" @default.
- W1865854714 modified "2023-09-27" @default.
- W1865854714 title "Abstract 1775: Identification of small molecule inhibitors of HSF1 stress pathway activation in cancer cells" @default.
- W1865854714 doi "https://doi.org/10.1158/1538-7445.am2014-1775" @default.
- W1865854714 hasPublicationYear "2014" @default.
- W1865854714 type Work @default.
- W1865854714 sameAs 1865854714 @default.
- W1865854714 citedByCount "0" @default.
- W1865854714 crossrefType "proceedings-article" @default.
- W1865854714 hasAuthorship W1865854714A5003965204 @default.
- W1865854714 hasAuthorship W1865854714A5006946698 @default.
- W1865854714 hasAuthorship W1865854714A5034700257 @default.
- W1865854714 hasAuthorship W1865854714A5052714030 @default.
- W1865854714 hasAuthorship W1865854714A5056212024 @default.
- W1865854714 hasAuthorship W1865854714A5058033074 @default.
- W1865854714 hasAuthorship W1865854714A5065737376 @default.
- W1865854714 hasAuthorship W1865854714A5075096091 @default.
- W1865854714 hasAuthorship W1865854714A5075359536 @default.
- W1865854714 hasAuthorship W1865854714A5084313119 @default.
- W1865854714 hasConcept C104317684 @default.
- W1865854714 hasConcept C121608353 @default.
- W1865854714 hasConcept C173396325 @default.
- W1865854714 hasConcept C185592680 @default.
- W1865854714 hasConcept C205260736 @default.
- W1865854714 hasConcept C2776667301 @default.
- W1865854714 hasConcept C2781452922 @default.
- W1865854714 hasConcept C502942594 @default.
- W1865854714 hasConcept C52981337 @default.
- W1865854714 hasConcept C54355233 @default.
- W1865854714 hasConcept C55493867 @default.
- W1865854714 hasConcept C555283112 @default.
- W1865854714 hasConcept C68991219 @default.
- W1865854714 hasConcept C86803240 @default.
- W1865854714 hasConcept C95444343 @default.
- W1865854714 hasConcept C96232424 @default.
- W1865854714 hasConceptScore W1865854714C104317684 @default.
- W1865854714 hasConceptScore W1865854714C121608353 @default.
- W1865854714 hasConceptScore W1865854714C173396325 @default.
- W1865854714 hasConceptScore W1865854714C185592680 @default.
- W1865854714 hasConceptScore W1865854714C205260736 @default.
- W1865854714 hasConceptScore W1865854714C2776667301 @default.
- W1865854714 hasConceptScore W1865854714C2781452922 @default.
- W1865854714 hasConceptScore W1865854714C502942594 @default.
- W1865854714 hasConceptScore W1865854714C52981337 @default.
- W1865854714 hasConceptScore W1865854714C54355233 @default.
- W1865854714 hasConceptScore W1865854714C55493867 @default.
- W1865854714 hasConceptScore W1865854714C555283112 @default.
- W1865854714 hasConceptScore W1865854714C68991219 @default.
- W1865854714 hasConceptScore W1865854714C86803240 @default.
- W1865854714 hasConceptScore W1865854714C95444343 @default.
- W1865854714 hasConceptScore W1865854714C96232424 @default.
- W1865854714 hasLocation W18658547141 @default.
- W1865854714 hasOpenAccess W1865854714 @default.
- W1865854714 hasPrimaryLocation W18658547141 @default.
- W1865854714 hasRelatedWork W1583990974 @default.
- W1865854714 hasRelatedWork W1836370442 @default.
- W1865854714 hasRelatedWork W2000560765 @default.
- W1865854714 hasRelatedWork W2013215178 @default.
- W1865854714 hasRelatedWork W2035428017 @default.
- W1865854714 hasRelatedWork W2038845293 @default.
- W1865854714 hasRelatedWork W2054854053 @default.
- W1865854714 hasRelatedWork W2055339736 @default.
- W1865854714 hasRelatedWork W2066003963 @default.
- W1865854714 hasRelatedWork W2074054154 @default.
- W1865854714 hasRelatedWork W2086384788 @default.
- W1865854714 hasRelatedWork W2112317481 @default.
- W1865854714 hasRelatedWork W2133121449 @default.
- W1865854714 hasRelatedWork W2153497725 @default.
- W1865854714 hasRelatedWork W2331428818 @default.
- W1865854714 hasRelatedWork W2485660542 @default.
- W1865854714 hasRelatedWork W2537067076 @default.
- W1865854714 hasRelatedWork W2558863919 @default.
- W1865854714 hasRelatedWork W2606644251 @default.
- W1865854714 hasRelatedWork W2966997471 @default.
- W1865854714 isParatext "false" @default.
- W1865854714 isRetracted "false" @default.
- W1865854714 magId "1865854714" @default.
- W1865854714 workType "article" @default.