The Hippo signalling pathway and its implications in human health and diseases

Abstract

As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in the regulation of numerous biological processes. Thus, substantial efforts have been made to understand the upstream signals that influence the activity of the Hippo pathway, as well as its physiological functions, such as cell proliferation and differentiation, organ growth, embryogenesis, and tissue regeneration/wound healing. However, dysregulation of the Hippo pathway can cause a variety of diseases, including cancer, eye diseases, cardiac diseases, pulmonary diseases, renal diseases, hepatic diseases, and immune dysfunction. Therefore, therapeutic strategies that target dysregulated Hippo components might be promising approaches for the treatment of a wide spectrum of diseases. Here, we review the key components and upstream signals of the Hippo pathway, as well as the critical physiological functions controlled by the Hippo pathway. Additionally, diseases associated with alterations in the Hippo pathway and potential therapies targeting Hippo components will be discussed.

Radiogenomics study to predict the nuclear grade of renal clear cell carcinoma

“…In addition, we constructed a hub mRNA model for predicting the nuclear grade. Biological processes always involve interactions among genes expressed by interaction networks which are controlled by driving hub genes [14] , [15] . Exploring the predictive performance of hub genes can help understand the association between radiomic features and genes.…”

The role of Hippo pathway in ferroptosis

“…After MST1/2 is activated by the upstream kinase thousand-and-one amino acid kinase (TAOK) ( 5 ) or dimerization itself ( 6 ), it can combine with SAV1 through its C-terminal Sav/RASSF/Hpo (SARAH) domain to phosphorylate SAV1 ( 2 ). Phosphorylated SAV1 can interact with LATS1/2 to assist LATS1/2 phosphorylation ( 7 ).…”

“…In addition to TEAD1–4, YAP can interact with Runx1/2, BRD4, Smad, and other transcription factors after entering the nucleus ( 2 , 10 , 20 ).…”

“…The Hippo pathway is mainly regulated by mechanical signal, cell polarity and cell connection, and G protein–coupled receptor (GPCR) ( 2 , 4 , 21 , 22 ) ( Figure 1 ).…”

Yes-Associated Protein and Transcriptional Coactivator with PDZ-Binding Motif in Cardiovascular Diseases

“…The latest research found that palmitoylation is an important protein modification mode of TEAD binding with the YAP/TAZ, and its unique binding mode makes the TEAD easy to target [ 160 ]. VT3989 and IK-930, two TEAD palmitoylation inhibitors, have been studied in human clinical trials [ 161 , 162 , 163 , 164 ]. Table 2 shows potential drugs targeting YAP/TAZ and its upstream and downstream pathways in pre-clinical trials and clinical trials.…”