Regulation of Tissue Growth by the Mammalian Hippo Signaling Pathway

Abstract

The integrative control of diverse biological processes such as proliferation, differentiation, apoptosis and metabolism is essential to maintain cellular and tissue homeostasis. Disruption of these underlie the development of many disease states including cancer and diabetes, as well as many of the complications that arise as a consequence of aging. These biological outputs are governed by many cellular signaling networks that function independently, and in concert, to convert changes in hormonal, mechanical and metabolic stimuli into alterations in gene expression. First identified in Drosophila melanogaster as a powerful mediator of cell division and apoptosis, the Hippo signaling pathway is a highly conserved regulator of mammalian organ size and functional capacity in both healthy and diseased tissues. Recent studies have implicated the pathway as an effector of diverse physiological cues demonstrating an essential role for the Hippo pathway as an integrative component of cellular homeostasis. In this review, we will: (a) outline the critical signaling elements that constitute the mammalian Hippo pathway, and how they function to regulate Hippo pathway-dependent gene expression and tissue growth, (b) discuss evidence that shows this pathway functions as an effector of diverse physiological stimuli and (c) highlight key questions in this developing field.

Interaction of S100A1 with LATS1 promotes cell growth through regulation of the Hippo pathway in hepatocellular carcinoma

“…It was demonstrated that S100A1 inactivated the Hippo signaling pathway. YAP, the downstream effector of Hippo signaling, is frequently overexpressed in various types of human cancer ( 30 ). The present study found that the depletion of S100A1 reduced total and nuclear YAP protein, and decreased TEAD luciferase reporter activity, serving as a marker of YAP downstream function ( 31 ).…”

Propofol Protects Hippocampal Neurons from Hypoxia‐Reoxygenation Injury by Decreasing Calcineurin‐Induced Calcium Overload and Activating YAP Signaling

“…However, the extracellular soluble regulators of YAP were barely known, until Yu et al found bioactive lipids, LPA, and sphingosine-1-phosphate (S1P) as extracellular regulators of YAP in mammary cell lines [ 37 ]. In addition, several hormones have been proved to regulate YAP, such as epinephrine, estrogen, and glucagon [ 38 ]. In the present study, we demonstrated that propofol acted as another extracellular soluble regulator of YAP.…”

Nuclear Functions of the Tyrosine Kinase Src

“…In the context of mechanobiology, the Hippo pathway has been described to be relevant in regulating tissue growth and organ size [74,75]. The main function of the Hippo pathway is to inhibit Yes-associated proiein (YAP) and Tafazzin (TAZ) transcription co-activators, thereby regulating cell proliferation, apoptosis, and stemness in response to extracellular and intracellular signals, among which cell-cell contact, cell polarity, mechanical cues, ligands of G-protein coupled receptors and cellular energy status [75].…”