Gokhale Rewatee, Pfleger Cathie M
Department of Oncological Sciences, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
The Graduate School of Biomedical Sciences, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Methods Mol Biol. 2019;1893:3-26. doi: 10.1007/978-1-4939-8910-2_1.
The Hippo Pathway comprises a vast network of components that integrate diverse signals including mechanical cues and cell surface or cell-surface-associated molecules to define cellular outputs of growth, proliferation, cell fate, and cell survival on both the cellular and tissue level. Because of the importance of the regulators, core components, and targets of this pathway in human health and disease, individual components were often identified by efforts in mammalian models or for a role in a specific process such as stress response or cell death. However, multiple components were originally discovered in the Drosophila system, and the breakthrough of conceiving that these components worked together in a signaling pathway came from a series of Drosophila genetic screens and fundamental genetic and phenotypic characterization efforts. In this chapter, we will review the original discoveries leading to the conceptual framework of these components as a tumor suppressor network. We will review chronologically the early efforts that established our initial understanding of the core machinery that then launched the growing and vibrant field to be discussed throughout later chapters of this book.
河马通路由大量的组件网络组成，这些组件整合了包括机械信号以及细胞表面或细胞表面相关分子在内的多种信号，以在细胞和组织水平上确定生长、增殖、细胞命运和细胞存活等细胞输出。由于该通路的调节因子、核心组件和靶点在人类健康和疾病中的重要性，单个组件往往是通过在哺乳动物模型中的研究工作或因其在诸如应激反应或细胞死亡等特定过程中的作用而被发现的。然而，多个组件最初是在果蝇系统中被发现的，而认识到这些组件在一条信号通路中协同工作这一突破则来自一系列果蝇遗传筛选以及基础遗传学和表型特征研究工作。在本章中，我们将回顾那些促成将这些组件视为肿瘤抑制网络的概念框架的最初发现。我们将按时间顺序回顾早期的研究工作，这些工作确立了我们对核心机制的初步认识，进而推动了这个不断发展且充满活力的领域，本书后续章节将对此进行讨论。
