Abstract A18: Location, location, location: Avenues to regulating Hippo

The TEAD family of the transcription factors (TEAD1-4) are the major transcription factors for YAP/TAZ transcription activators in the Hippo pathway. TEADs regulate many biologic processes, including development, tissue homeostasis, and tumorigenesis by regulating target genes involved in cellular proliferation and survival. Amplification or upregulation of YAP/TAZ/TEAD correlates with poor prognosis in cancer patients. The mechanisms of TEADs regulation and localization remain largely unknown. TEADs contain a highly conserved nuclear localization signal (NLS) embedded in the DNA binding domain (DBD). Overexpression of an NLS mutant TEAD in a Hippo-dependent cancer cell line is dominant negative and suppresses cellular proliferation and tumor growth. These results suggest that TEAD nuclear expression is regulated by a highly conserved NLS that may be important in the development of cancer. In light of these results, we have identified physiologic conditions where TEADs are expressed in the cytoplasm and the nucleus. By performing comparative immunoprecipitation-mass spectrometry between WT and NLS mutant TEAD, we found novel interacting partners for cytoplasmic and nuclear TEAD, thus uncovering novel roles for TEADs in cancer. Citation Format: Philamer C. Calses, Victoria Pham, Erik Verschueren, Noelyn Kljavin, Matt Chang, Kerstin Seidel, Benjamin Haley, Trang Pham, Cameron Noland, Trent Hinkle, Thijs Hagenbeek, Jennie Lill, Anwesha Dey. Location, location, location: Avenues to regulating Hippo [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 A18.