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Journal Article
The Hippo pathway in intestinal regeneration and disease
2016
Overview
Key Points
The Hippo pathway plays an important part in intestinal homeostasis and regeneration in both
Drosophila melanogaster
and mammals, and its dysregulation often leads to uncontrolled tissue growth
In general, YAP1 and TAZ activity promotes intestinal stem cell properties, and overexpression of YAP1 induces stem cell expansion
YAP1 and TAZ are crucial for intestinal tissue regeneration after injury; YAP1 depletion leads to disturbed tissue formation during regeneration
Crosstalk between the Hippo pathway and other signalling pathways, such as Wnt and Notch, regulates intestinal tissue homeostasis and regeneration, although detailed mechanisms have not yet been elucidated
Dysregulation of the Hippo pathway leads to tumorigenesis;
YAP1
and
TAZ
are oncogenic in colorectal cancers, as illustrated by data from mouse models and patient specimens
The Hippo pathway also has an important role in liver damage repair and tumorigenesis, and dysregulation of the Hippo pathway leads to uncontrolled growth in the liver
The Hippo signalling cascade is crucial for the maintenance of tissue homeostasis and regeneration after damage. This Review describes the core components of the Hippo pathway and their role in intestinal homeostasis, regeneration and disease, and the integration of Hippo signalling with other key signalling pathways. The function of the Hippo pathway in liver physiology and disease is briefly discussed.
The Hippo pathway is a signalling cascade conserved from
Drosophila melanogaster
to mammals. The mammalian core kinase components comprise MST1 and MST2, SAV1, LATS1 and LATS2 and MOB1A and MOB1B. The transcriptional co-activators YAP1 and TAZ are the downstream effectors of the Hippo pathway and regulate target gene expression. Hippo signalling has crucial roles in the control of organ size, tissue homeostasis and regeneration, and dysregulation of the Hippo pathway can lead to uncontrolled cell growth and malignant transformation. Mammalian intestine consists of a stem cell compartment as well as differentiated cells, and its ability to regenerate rapidly after injury makes it an excellent model system to study tissue homeostasis, regeneration and tumorigenesis. Several studies have established the important role of the Hippo pathway in these processes. In addition, crosstalk between Hippo and other signalling pathways provides tight, yet versatile, regulation of tissue homeostasis. In this Review, we summarize studies on the role of the Hippo pathway in the intestine on these physiological processes and the underlying mechanisms responsible, and discuss future research directions and potential therapeutic strategies targeting Hippo signalling in intestinal disease.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 64/24
/ Adaptor Proteins, Signal Transducing - metabolism
/ Animals
/ Bone Morphogenetic Proteins - metabolism
/ Cellular signal transduction
/ Colonic Neoplasms - physiopathology
/ Hedgehog Proteins - metabolism
/ Humans
/ Intestine, Large - physiology
/ Intestine, Small - physiology
/ Irritable Bowel Syndrome - physiopathology
/ Liver Neoplasms - physiopathology
/ Mammals
/ Phosphoproteins - metabolism
/ Protein-Serine-Threonine Kinases - metabolism
/ Receptors, G-Protein-Coupled - physiology
/ Receptors, Notch - metabolism
/ Signal Transduction - physiology
/ Stress, Physiological - physiology
