Hippo Signaling Pathway and Cancer: Molecular Regulation and Therapeutic Targets

Abstract

: The Hippo signaling pathway is one of the critical regulators of organ growth and proliferation. This pathway was first described in Drosophila, and now it is identified as one of the most conserved molecular pathways in all multicellular organisms. Recent studies have shown that the dysregulation of the Hippo pathway is associated with various cancers, contributing to tumorigenesis and cancer progression. Numerous attempts have been made to target the major components of this pathway for therapeutic interventions. YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ binding motif) molecules are the critical components involved in the Hippo pathway. These factors have been identified as essential in the incidence and progression of cancer and drug resistance. The intracellular localization of YAP/TAZ is a crucial regulator of its activity, i.e., activating the transcription of their target genes and, eventually, the possible development of cancer. The abundance of YAP/TAZ in the nucleus has been observed in many human cancers. Therefore, recent research has investigated direct and indirect therapeutic approaches to inhibit this localization. This study describes the Hippo signaling pathway, its components, molecular regulation, and involvement in cancer development. Finally, we examine new therapeutic targets aimed at regulating this pathway.