New Insights into the Roles of the Hippo Signaling Pathway in Stem Cell Biology

A highly conserved kinase cascade, including mammalian STE20-like protein kinases (MSTs), large tumor suppressors (LATSs), and downstream transcription coactivators containing YES-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are involved in the Hippo signaling pathway. As two critical transcriptional coactivators, TAZ and YAP are adversely regulated by the Hippo signaling pathway. They lead to the induction of organ regeneration and the expression of cell growth and division-promoting genes through binding to transcription factors, especially TEA domain transcription factors (TEADs). Previous studies highlight the role of the Hippo pathway in organ size control, homeostasis, cell proliferation, and tumor development. Research has shown this pathway's vital role in cancer stem cell biology, including self-renewal and drug resistance. Improper activation of YAP and TAZ through the Hippo pathway dysregulation or its increased expression can accelerate tumorigenesis. Thus, pharmacological inhibition of YAP and TAZ is suggested as a promising approach in the treatment of tumors with high YAP/TAZ activity.