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- W1564563558 abstract "The long-term survival of patients with glioblastoma (GB) is compromised by the proclivity for local invasion into the surrounding normal brain, escaping surgical resection and contributing to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell invasion via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB. In order to discover a small molecule inhibitors that disrupt Fn14-TWEAK signaling axis and subsequently glioma cell invasion, we developed a cell-based drug screening assay using HEK293 cells that overexpresses Fn14 and harbors NF-κB driven Firefly luciferase protein expression. In preliminary drug screening assay using LOPAC1280 library of 1280 pharmacologically active compound, Aurintricarboxylic Acid (ATA) showed suppression of NF-κB driven Firefly Luciferase activity downstreatm of TWEAK-Fn14 signaling. Conversely, ATA did not show any suppression in NF-κB driven Firefly Luciferase activity downstream of TNFα-TNFR1 signaling, suggesting that ATA is a specific inhibitor of TWEAK-Fn14-NF-κB signaling. In vitro, we demonstrated that ATA suppresses TWEAK induced chemotactic migration of glioma cells (T98G and A172) and display no general cytotoxicity. In summary, this work reports a new small molecule inhibitor of TWEAK-Fn14 signaling that could be useful in enhancing the therapeutic targeting of this deadly disease. Citation Format: Harshil D. Dhruv, Ethan Holiday, Donald Chow, Holly Yin, Michael E. Berens, Nhan L. Tran. Identification of Aurintricarboxylic Acid (ATA) as an inhibitor of TWEAK-Fn14 signaling in glioblastoma 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 2709. doi:10.1158/1538-7445.AM2014-2709" @default.
- W1564563558 created "2016-06-24" @default.
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- W1564563558 date "2014-09-30" @default.
- W1564563558 modified "2023-09-22" @default.
- W1564563558 title "Abstract 2709: Identification of Aurintricarboxylic Acid (ATA) as an inhibitor of TWEAK-Fn14 signaling in glioblastoma cells" @default.
- W1564563558 doi "https://doi.org/10.1158/1538-7445.am2014-2709" @default.
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