Hippo signaling pathway

Thus, the delineation of the pathway in Drosophila has helped to identify many genes that function as oncogenes or tumor suppressors in mammals.

This highly conserved group of serine/threonine kinases regulates several cellular processes, including cell proliferation, apoptosis, and various stress responses.

[9] Two proteins are known to facilitate the activation of Wts: Salvador (Sav) and Mob as tumor suppressor (Mats).

In its active state, Yki binds to the transcription factor Scalloped (Sd), and the Yki-Sd complex becomes localized to the nucleus.

[13] Yki also activates expression of the bantam microRNA, a positive growth regulator that specifically affects cell number.

In mammals, the two Yki orthologs are Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (WWTR1, also known as TAZ).

As an atypical cadherin, Fat (FAT1-4 in mammals) may function as a receptor, though an extracellular ligand has not been positively identified.

[25] Many of the genes involved in the Hippo signaling pathway are recognized as tumor suppressors, while Yki/YAP/TAZ is identified as an oncogene.

[27][28][29] This may be explained by YAP’s recently defined role in overcoming contact inhibition, a fundamental growth control property of normal cells in vitro and in vivo, in which proliferation stops after cells reach confluence[30] (in culture) or occupy maximum available space inside the body and touch one another.

[35][36] However, recent research by Marc Kirschner and Taran Gujral has demonstrated that Hippo pathway components may play a more nuanced role in cancer than previously thought.

Hippo pathway inactivation enhanced the effect of 15 FDA-approved oncology drugs by promoting chemo-retention.

In hepatocellular carcinoma, for instance, it was suggesting that AXIN1 mutations would provoke Hippo signaling pathway activation, fostering the cancer development, but a recent study demonstrated that such an effect cannot be detected.

Loss of cardiomyocytes because of injury or diseases leads to heart failure, which is a major cause of human morbidity and mortality.

Inactivation of the Hippo pathway or activation of its downstream effector, the Yes-associated protein transcription coactivator, improves cardiac regeneration.

In addition, Yes-associated protein has been shown to regulate cardiomyocyte fate through multiple transcriptional mechanisms.