The Hippo Pathway as Drug Targets in Cancer Therapy and Regenerative Medicine

Abstract

Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) co-operate with numerous transcription factors to regulate gene transcriptions. YAP1 and TAZ are negatively regulated by the tumor suppressive Hippo pathway. In human cancers, the Hippo pathway is frequently deregulated and YAP1 and TAZ escape the inhibition by the Hippo pathway. The upregulation of YAP1 and TAZ induces epithelial-mesenchymal transition and increases drug resistance in cancer cells. TAZ is implicated in cancer stemness. In consequence cancers with hyperactive YAP1 and TAZ are associated with poor clinical prognosis. Inhibitors of YAP1 and TAZ are reasoned to be beneficial in cancer therapy. On the other hand, since YAP1 and TAZ play important roles in the regulation of various tissue stem cells and in tissue repair, activators of YAP1 and TAZ are useful in the regenerative medicine. We discuss the potential application of inhibitors and activators of YAP1 and TAZ in human diseases and review the progress of drug screenings to search for them.

TAZ and myostatin involved in muscle atrophy of congenital neurogenic clubfoot

“…Our previous studies confirmed that TAZ and its activator promoted muscle differentiation and resisted muscular atrophy, based on in vivo animal models of muscular atrophy induced by toxins, glucocorticoids[10], traumatic brain injury[16], disuse, starvation, and cancer-related cachexia[30]. These results suggest the potential of TAZ activators for treatment of muscle atrophy.…”

Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review

“…This protein, along with its partner PDZ-binding domain taffazin, orchestrate the Hippo pathway[ 147 ]. In principle, hippo signalling plays an important role in the regulation of tissue homeostasis, development, regeneration, and cancer[ 148 ]. Three protein components in mammals are depicted: Mammalian Ste 2 like kinase 1 and 2, and large tumor suppressor kinase 1 and 2.…”

Hippo signaling pathway transcription co-activator YAP is localized to podosomes/invadopodia in Src-transformed NIH-3T3 fibroblasts      

“…If yes, it would be important to check if other components of the Hippo signaling pathway are also involved in the formation of invadopodia. This could constitute another mechanism through which the Hippo signaling pathway impinges on cancer cell organization and metastasis [8] [9].…”