Abstract IA11: Hippo signaling Is Intrinsically regulated during cell cycle progression

Abstract

Abstract The Hippo-YAP/TAZ signaling pathway plays a pivotal role in growth control during development and regeneration, and its dysregulation is widely implicated in various cancers. Hippo signaling has been recently identified as a major oncosuppressive pathway that plays critical roles in inhibiting hepatocyte proliferation, survival, and hepatocellular carcinoma (HCC) formation. We have found that Hippo/YAP signaling cell-autonomously inhibits HCC proliferation by interacting with Wnt and Notch signaling. We have also found that Hippo/YAP signaling cell-nonautonomously inhibits HCC by shaping its inflammatory microenvironment. To further understand the cellular and molecular mechanisms underlying Hippo signaling regulation, we have found that activities of core Hippo signaling components, LATS kinases and YAP/TAZ transcription factors, are regulated during cell cycle progression by core cell cycle machinery components. Furthermore, we show in Drosophila eye and wing development that cell cycle is required in vivo to regulate Hippo signaling with a conserved mechanism. Cell cycle control of Hippo signaling represents a previously unappreciated and evolutionarily conserved new layer of Hippo signaling regulation. Citation Format: Yingzi Yang, Wantae Kim, Xiaohui Wang. Hippo signaling Is Intrinsically regulated during cell cycle progression [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 IA11.