Show simple item record

dc.contributor.authorRoos, A.
dc.contributor.authorDhruv, H.D.
dc.contributor.authorMathews, I.T.
dc.date.accessioned2019-07-15T16:17:01Z
dc.date.available2019-07-15T16:17:01Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85012928601&doi=10.18632%2foncotarget.14685&partnerID=40&md5=d43c3eda0e6bae9387e79a1489941d72
dc.identifier.urihttp://hdl.handle.net/10713/10058
dc.description.abstractThe survival of patients diagnosed with glioblastoma (GBM), the most deadly form of brain cancer, is compromised by the proclivity for local invasion into the surrounding normal brain, which prevents complete surgical resection and contributes to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) superfamily, can stimulate glioma cell invasion and survival via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB. To discover small molecule inhibitors that disrupt the TWEAK-Fn14 signaling axis, we utilized a cell-based drug-screening assay using HEK293 cells engineered to express both Fn14 and a NF-κB-driven firefly luciferase reporter protein. Focusing on the LOPAC1280 library of 1280 pharmacologically active compounds, we identified aurintricarboxylic acid (ATA) as an agent that suppressed TWEAK-Fn14-NF-κB dependent signaling, but not TNFα-TNFR-NF-κB driven signaling. We demonstrated that ATA repressed TWEAK-induced glioma cell chemotactic migration and invasion via inhibition of Rac1 activation but had no effect on cell viability or Fn14 expression. In addition, ATA treatment enhanced glioma cell sensitivity to both the chemotherapeutic agent temozolomide (TMZ) and radiation-induced cell death. In summary, this work reports a repurposed use of a small molecule inhibitor that targets the TWEAK-Fn14 signaling axis, which could potentially be developed as a new therapeutic agent for treatment of GBM patients.en_US
dc.description.sponsorshipThis work was supported by NIH grant R01 CA130940 and The Ben and Catherine Ivy Foundation.en_US
dc.description.urihttps://www.doi.org/10.18632/oncotarget.14685en_US
dc.language.isoen_USen_US
dc.publisherImpact Journals LLCen_US
dc.relation.ispartofOncotarget
dc.subjectAurintricarboxylic aciden_US
dc.subjectFn14en_US
dc.subjectGlioblastomaen_US
dc.subjectInvasionen_US
dc.subjectSurvivalen_US
dc.titleIdentification of aurintricarboxylic acid as a selective inhibitor of the TWEAK-Fn14 signaling pathway in glioblastoma cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.18632/oncotarget.14685
dc.identifier.pmid28103571


This item appears in the following Collection(s)

Show simple item record