Aug 2026· Cold Spring Harbor Perspectives in Biology· 0 citations
Medicine
TL;DR
The spatiotemporal control of core pathway components in murine and human lungs is reviewed, highlighting how YAP and TAZ integrate mechanical and molecular cues to govern epithelial patterning, mesenchymal function, vascular integrity, and stem cell behavior.
Abstract
The Hippo signaling pathway and its effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) have emerged as central regulators of respiratory biology, playing essential functions in the development, homeostasis, and regeneration of the lung and trachea. Here, we review the spatiotemporal control of core pathway components in murine and human lungs, highlighting how YAP and TAZ integrate mechanical and molecular cues to govern epithelial patterning, mesenchymal function, vascular integrity, and stem cell behavior. We provide an overview of the mechanisms by which Hippo-YAP/TAZ signaling directs lung injury repair, while also exploring how its dysregulation contributes to fibrosis, vascular remodeling, and lung tumorigenesis. Finally, we discuss the importance of restoring or targeting YAP/TAZ-TEAD activity in the lung and consider the opportunities and challenges associated with pharmacologic inhibition in pulmonary disease.
This review provides an updated overview of this transcriptional module within the Hippo pathway, discusses how it modulates gene transcription to contribute to development and disease, and proposes outstanding questions that warrant further investigation in future studies.
Xiao-Lei Cao, Mei Tang, Zezhen Lu et al.· Cold Spring Harbor Perspecti...· 0 citations
This review delineates the biological functions of the Hippo–YAP/TAZ–TEAD axis and integrate its pathway physiology with the structural basis of druggability, centered on the Ω‐loop surface pocket and the buried palmitoylation‐binding pocket of TEAD, whose distinct geometries dictate the pharmacophoric requirements, pa...
Vascular homeostasis depends on coordinated responses among endothelial cells, vascular smooth muscle cells, and perivascular cells. The Hippo pathway effectors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) integrate mechanical, metabolic, and biochemical cues within these ce...
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A unified mechanistic framework by which the level of YAP/TAZ activity determines enhancer landscapes that favor either differentiated or progenitor-like cellular states is proposed, providing a potential basis for applications to regenerative medicine and therapeutic interventions.
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The interplay between YAP/TAZ and metabolic reprogramming in cancer is systematically clarified, the core molecular networks through which YAP/TAZ govern each metabolic pathway are delineated, and the current pharmacological inhibitors targeting YAP/TAZ-regulated metabolic networks are summarized.
Yin-Huang Gao, Ming-Hong Chen, Song-Xia Lin et al.· International Journal of Mol...· 0 citations
This review summarizes recent advances in how NF2 regulates YAP/TAZ and AMOT functions, focusing on their roles in tumor formation, metastasis, and angiogenesis.
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