Abstract
Initially identified in Drosophila, the Hippo signaling pathway has emerged as an evolutionarily conserved tumor suppressor pathway that controls tissue growth and organ size by simultaneously inhibiting cell proliferation and promoting cell death. Deregulation of Hippo pathway activity has been implicated in a wide range of human cancers. The core Hippo pathway consists of a kinase cascade: an upstream kinase Hippo (Hpo)/MST1/2 phosphorylates and activates a downstream kinase Warts (Wts)/Lats1/2, leading to phosphorylation and inactivation of a transcriptional coactivator Yki/YAP/Taz. Many upstream signals, including cell adhesion, polarity, mechanical stress, and soluble factors, regulate Hippo signaling through the kinase cascade, leading to change in the cytoplasmic/nuclear localization of Yki/YAP/Taz. However, recent studies have uncovered other mechanisms that regulate Yki/YAP/Taz subcellular localization, stability, and activity independent of the Hpo kinase cascade. These mechanisms provide additional layers of pathway regulation, nodes for pathway crosstalk, and opportunities for pathway intervention in cancer treatment and regenerative medicine.
Highlights
The regulation of cell growth, proliferation, and cell death is tightly controlled during embryonic development and adult tissue homeostasis by environmental cues such as morphogens, cytokines, hormonal signals, and nutrients and by cell-intrinsic mechanisms
The Hippo signaling pathway, which was initially identified in Drosophila, has emerged as an evolutionarily conserved tumor suppressor pathway that regulates tissue growth and organ size in a wide range of species ranging from insects to humans (Pan, 2007; Zhang et al, 2009; Halder and Johnson, 2011)
We focus on recent studies that uncover additional mechanisms that control Yki/Yes-associated protein (Yap)/Transcriptional activator with PDZ-binding motif (Taz) activity independent of the Hpo kinase cascade
Summary
The regulation of cell growth, proliferation, and cell death is tightly controlled during embryonic development and adult tissue homeostasis by environmental cues such as morphogens, cytokines, hormonal signals, and nutrients and by cell-intrinsic mechanisms. The Hippo signaling pathway, which was initially identified in Drosophila, has emerged as an evolutionarily conserved tumor suppressor pathway that regulates tissue growth and organ size in a wide range of species ranging from insects to humans (Pan, 2007; Zhang et al, 2009; Halder and Johnson, 2011). Deregulation of Hippo pathway activity has been implicated in many types of human cancer and other diseases (Yu et al, 2015; Zanconato et al, 2016; Zheng and Pan, 2019). Hippo-Independent Regulation of Yap/Taz downstream of the core Hippo signaling pathway to modulate pathway outputs. We discuss how these findings inform us about new strategies for cancer treatment and regenerative medicine
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
