Linking EMT Dynamics to Cellular Plasticity: YAP/TAZ as Central Regulators Across Physiological and Pathological States.

Cellular plasticity allows organisms to adapt dynamically to both physiological and pathological contexts. Epithelial-mesenchymal transition (EMT) is a well-known example of this plasticity and is now widely recognized as a reversible and highly dynamic spectrum of cellular states rather than a simple binary switch. In this review, we summarize current knowledge on the Hippo pathway transcriptional co-activators YAP and TAZ, focusing on their role as a central hub that integrates mechanical, biochemical and metabolic signals from the microenvironment to control cell fate reprogramming. We discuss how YAP/TAZ interact with EMT-related signaling pathways and transcriptional networks to regulate the acquisition, maintenance and dynamic remodeling of mesenchymal states, as well as hybrid epithelial/mesenchymal (E/M) phenotypes. We also highlight the presence of interconnected feed-forward and feedback regulatory loops within the YAP/TAZ-EMT axis, which contribute to the stabilization of cellular plasticity and support context-dependent transcriptional programs. These mechanisms are involved in key physiological processes, including embryonic development and tissue repair, and in pathological conditions such as organ fibrosis and cancer progression. Therefore, we propose a model where YAP/TAZ act as the central molecular hub within the networks governing cellular plasticity and EMT dynamics. Finally, we discuss how a better understanding of the mechanistic basis of YAP/TAZ-driven EMT may provide a useful framework for the development of therapeutic strategies aimed at modulating cellular plasticity in cancer, fibrotic diseases and regenerative medicine.