Abstract B12: High-throughput screening platform to discover TEAD modulators

The TEAD family of transcription factors play critical roles during development, cell growth, proliferation, regeneration, and tissue homeostasis. TEADs are key downstream transcription factors of the evolutionarily conserved Hippo pathway, which binds Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ) transcriptional coactivators through their transactivation domains. Despite TEAD being the key transducer of the Hippo signaling, most research have been focused on Hippo kinases and YAP/TAZ, whereas the Hippo-dependent and -independent regulators and regulations governing TEAD emerged only recently. Previously, we identified that environmental stress promotes TEAD cytoplasmic translocation via p38 MAPK-dependent, Hippo-independent mechanism, which overrides YAP-driven oncogenic growth in cancer cells. Here, we present a platform for high-throughput screening to identify chemical compounds that modulate TEAD cellular localization and activity. We designed cancer cells stably expressing a TEAD-GFP lentiviral vector and carried out a comprehensive comparative analysis of TEAD4 by GFP-fluorescence, immunoblotting, and transcript activities. Chemical compound screening to discover TEAD modulators will reveal novel anticancer drugs. Citation Format: Sungho Moon, Hyun Woo Park. High-throughput screening platform to discover TEAD modulators [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B12.