Control of growth and beyond: a special issue on Hippo signaling.

Abstract

That the Hippo signaling controls organ size was first recognized almosta decadeago.Hipposignalinghasbeendemonstrated asa master regulator in diverse developmental processes. Its malfunction induces mis-regulated organ growth and tumorigenesis. Hippo signaling research has attracted increasing attention worldwide leading to a rapidly evolving of the emerging field. The ChineseHippoConsortiumhasbeenset upbyagroupofleading scientist from top institutes and universities in China. The consortium not only provides a platform for Chinese researchers who are interested in studying Hippo signaling to share resources and communicate ideas but also promotes collaboration. We invited eight leading Chinese researchers who are Chinese Hippo Consortium members to contribute to this special issue by highlighting topics that they think are the burgeoning interests in Hippo signaling. We are happy to present you eight review articles that illustrate some key trends in the area of Hippo signaling. The articles included cover the regulation and the function of the Hippo pathway in regulating organsize, cancer progression, and tissue regeneration as well as its roles in mammalianadaptive immunity. Although the subjects covered in these reviews are not comprehensive, we have attempted to cover the up-to-date key findings of this field. In their review, Yuan and colleagues discuss how Hippo signaling responds to cellular stress and hence maintain homeostasis, while Lei and colleagues focus on the bridge from the extracellular signalsto the Hippo pathway. The Hippo pathway controls diverse developmental processes through the regulation of its downstream effector Yorkie/ YAP. As reviewed by Zhao and colleagues, YAP is tightly regulated by various mechanisms in organ size control, regeneration and tumorigenesis, while it is not yet completely clear how YAP is coordinately regulated by physical signals, matrix stiffness and chemical signals. To help further understand the function of proteins, structural information may help. Zhou and colleagues provide a structural dissection of Hippo signaling to discuss the regulatory mechanisms underlying Hippo signaling derived from structural aspect. Much work is currently focusing on the function of Hippo signalingin stem cellbiologyandtumorigenesis: understanding howthe correct signaling levels are maintained to allow sufficient developmental growth and adult homeostasis, while preventing disease and tumor formation. Yin and Zhang discuss the roles of Hippo signaling in its roles in regulating stem cells in epithelial tissues and its potential implications in related cancers. Zhou and colleagues give more specific details regarding Hippo signaling in liver growth and liver cancers, while Shi and Chen describe its roles in mammary gland development and breast cancer. Though the initial work in Drosophila focused on the roles of Hipposignaling in developmentalsizecontrol, multiple non-canonical Hippo signaling pathways have turned out to implicate in the regulation of various other biological processes. In their review, Tao and colleagues discuss the roles of non-canonical Hippo signaling in lymphocyte developmentandfunctions. Researchreviewedin thisspecial issue indicates that Hippo signaling is an important regulator of various diseases and cancers. Targeting this signaling pathway may hopefully pave the way to new therapeutic interventions. To conclude, this issue coversthe major topics in the field of Hippo signaling and provides up-to-date information in this field. We hope you will enjoy and benefit from the topics that we cover in this special