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. 2021 Dec;41(1):172-180.
doi: 10.1080/01652176.2021.1923085.

Hippo signaling pathway in companion animal diseases, an under investigated signaling cascade

Affiliations

Hippo signaling pathway in companion animal diseases, an under investigated signaling cascade

Shaydee J Budel et al. Vet Q. 2021 Dec.

Abstract

The Hippo pathway is a highly conserved kinase cascade in mammals with the proteins YAP and TAZ as its most important downstream effectors that shuttle between cytoplasma and nucleus. It has a crucial role in processes such as embryogenesis, organ size control, homeostasis and tissue regeneration, where mechanosensing and/or cell-cell interactions are involved. As the pathway is associated with many essential functions in the body, its dysregulation is related to many diseases. In contrast to human pathology, a PubMed-search on Hippo, YAP/TAZ and companion animals (horse, equine, dog, canine, cat, feline) retrieved few publications. Because of its high level of functional conservation, it is anticipated that also in veterinary sciences aberrant Hippo YAP/TAZ signaling would be implicated in animal pathologies. Publications on Hippo YAP/TAZ in companion animals are mainly in cats and dogs and related to oncology. Here, we emphasize the important role of YAP/TAZ in liver diseases. First the liver has a remarkable regeneration capacity and a strict size control and the liver has a moderate liver cell renewal (homeostasis). The last years numerous papers show the importance of YAP/TAZ in hepatocellular carcinoma (HCC), hepatocyte differentiation and bile duct epithelial (BEC) cell survival. YAP/TAZ signaling is involved in activation of hepatic stellate cells crucial in fibrogenesis. The availability of drugs (e.g. verteporfin) targeting the YAP/TAZ pathway are described as is their potential usage in veterinary medicine. The aim of this overview is to stimulate researchers' and clinicians' interest in the potential role of Hippo YAP/TAZ signaling in veterinary medicine.

Keywords: Equine; Hippo pathway; YAP/TAZ signaling; canine; feline; liver; mammary gland; verteporfin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
(A) Hippo On. Upon a plethora of external signals, such as G-protein coupled receptors, cell-adhesion, and (mechano)stress, MST1/2 (mammalian homologue of Drosphilia Hippo), and SAV1 are phosphorylated upon which LATS1/2-MOB protein become phosphorylated. This leads to phosphorylation of YAP/TAZ, that upon binding to 14-3-3 proteins degrades. (B) Hippo OFF. Due to lack of stimuli on MST1/2-SAV1, these protein remain unphosphorylated, as well as downstream proteins LATS1/2-MOB and YAP/TAZ. Unphosphorylated YAP/TAZ can enter the nucleus where, upon interaction ioth TEAD dries the transcription of specific gene products, such as cyr61, ctgf and nuak2.

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