Hippo in Gastric Cancer: From Signalling to Therapy

SIMPLE SUMMARY: The Hippo signalling pathway is one of the most crucial and complex ones in physiology, and there is no doubt that the regulatory mechanisms it possesses are various. The role of this signalisation process in tissue homeostasis makes it keen to lead to cancerous processes when dysregulated. This review relates Hippo signalling and, more particularly, its role in gastric carcinogenesis and what has been attempted until today to encounter its disruption in this context. The Hippo pathway effectors YAP and TAZ are found to have a particularly important role in this disease. Different strategies, which can be used for their targeting in the GC context, are related in this review, may they be through their direct inhibition or through the activation of upstream Hippo kinases. Understanding the dysregulation of the organ homeostasis-regulating pathway in the cancer context is an important step towards the development of anti-gastric cancer therapeutical strategies. ABSTRACT: The Hippo pathway is one of the most important ones in mammals. Its key functions in cell proliferation, tissue growth, repair, and homeostasis make it the most crucial one to be controlled. Many means have been deployed for its regulation, since this pathway is not only composed of core regulatory components, but it also communicates with and regulates various other pathways, making this signalisation even more complex. Its role in cancer has been studied more and more over the past few years, and it presents YAP/TAZ as the major oncogenic actors. In this review, we relate how vital this pathway is for different organs, and how regulatory mechanisms have been bypassed to lead to cancerous states. Most studies present an upregulation status of YAP/TAZ, and urge the need to target them. A focus is made here on gastric carcinogenesis, its main dysregulations, and the major strategies adopted and tested to counteract Hippo pathway disbalance in this disease. Hippo pathway targeting can be achieved by various means, which are described in this review. Many studies have tested different potential molecules, which are detailed hereby. Though not all tested in gastric cancer, they could represent a real interest.