Signal Transduction and Targeted Therapy: The Hippo signaling pathway and its significance in human health and disease

The hippo pathway was first discovered in Drosophila melanogastera and has been studied
for the past 20 years.
A timeline
of the basic discovery and process of the HIPPO pathway.
In mammals, the Hippo pathway consists of several key components, including mammalian STE20-like kinase 1/2 (MST1/2), protein Salvador homologue 1 (SAV1), MOBKL1A/B (MOB1A/B), large tumor suppressor 1/2 (LATS1/2), YesAssociated Protein 1 (YAP), transcriptional regulator 1 (TAZ) containing WW domains, and transcription-enhancing associated domains ( TEAD) family
.

YAP/TAZ are transcriptional coactivators that bind to TEAD1-4 and regulate the expression of a range of genes that mediate cell proliferation, apoptosis, and stem cell self-renewal
.
In addition, multiple upstream signals, such as cell polarity, mechanical signaling, cell density, soluble factor, and stress signaling, regulate the Hippo pathway
.

Image source: https://doi.
org/10.
1038/s41392-022-01191-9

Researchers from Sichuan University have published a review article titled "The Hippo signalling pathway and its implications in human health and diseases" in the journal Signal Transduction and Targeted Therapy, which summarizes the Hippo signaling pathway and its significance in human health and disease
。

As an evolutionarily conserved signaling network, the Hippo pathway plays a crucial role
in the regulation of many biological processes.
Therefore, a lot of research has been carried
out on upstream signals that affect the activity of the Hippo pathway and its physiological functions, such as cell proliferation and differentiation, organ growth, embryogenesis, tissue regeneration/wound healing, etc.

However, dysregulation of the Hippo pathway can lead to a variety of diseases, including cancer, eye disease, heart disease, lung disease, kidney disease, liver disease, and immune dysfunction
.
Therefore, therapeutic strategies targeting the dysregulated Hippo component may be a promising approach
to treating a wide range of diseases.
In this study, the researchers reviewed the key components and upstream signaling of the Hippo pathway, as well as the key physiological functions
controlled by the Hippo pathway.
In addition, diseases associated with altered Hippo pathways and potential treatments
targeting Hippo components will be discussed.

The core hippo pathway in mammals

Image source: https://doi.
org/10.
1038/s41392-022-01191-9

As a result of extensive basic research, key components of the Hippo pathway network have been identified, including MST1/2, LATS1/2, MOB1A/B, SAV1, YAP/TAZ and TEAD1-4
.
In addition, other proteins such as NF2, MAP4Ks and WWC1/2/3 are important components of
the hippopotamus pathway.

The main components and regulatory mechanisms of the HIPPO pathway are in place
.
The discovery of new ingredients may further improve our understanding
of the Hippo pathway in many physiological and pathological processes.
Furthermore, although some upstream signals have been shown to affect the activity of the Hippo pathway, a comprehensive and nuanced explanation of how these upstream signals are delivered to Hippo components is not entirely clear
.

Furthermore, since the hippo pathway is involved in the regulation of many key physiological processes, such as cell proliferation and differentiation, embryonic development, and tissue regeneration, it is not surprising that dysregulation of the hippo pathway is associated with a range of pathological consequences
.
As a result, many treatments targeting Hippo core enzyme, YAP/TAZ or TEAD have been suggested for the treatment
of various diseases.
(Biovalley Bioon.
com)

References

Minyang Fu et al.
The Hippo signalling pathway and its implications in human health and diseases.
Signal Transduct Target Ther.
2022 Nov 8; 7(1):376.
doi: 10.
1038/s41392-022-01191-9.