Abstract IA17: Hippo pathway deregulation in cancers

Abstract

Abstract The Hippo signaling pathway is an evolutionarily conserved pathway that plays a key role in the development and homeostasis of tissues and organs. The TEAD family of the transcription factors (TEAD1-4) are the major transcription factors, and YAP/TAZ are the transcription activators/ key effectors of 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/TEADs correlates with poor prognosis in cancer patients. While data over the past few years have demonstrated that the pathway is dysregulated in a spectrum of cancers, the underlying molecular mechanisms of regulation and localization are areas of active investigation. One such focus area that I will discuss during my talk is the regulation and localization of TEADs. 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. Additionally, 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: Anwesha Dey. Hippo pathway deregulation in cancers [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 IA17.