YAP/TAZ-TEAD

YAP/TAZ-TEAD is the principal transcriptional effector module of the Hippo signaling pathway and regulates organ size control, cell proliferation, apoptosis, stem cell properties, and tissue homeostasis through context-dependent transcriptional programs^[1][2]. When Hippo signaling is active, LATS kinases phosphorylate YAP and TAZ, restricting their nuclear localization and limiting TEAD-dependent gene expression; conversely, Hippo pathway inactivation allows YAP/TAZ nuclear accumulation and binding to TEAD1-4, thereby activating transcriptional programs associated with cellular growth and survival^[2][3][4]. Mechanistically, the YAP/TAZ-TEAD complex integrates biochemical and mechanical signals from the cellular microenvironment to control epithelial cell behavior, regeneration, and contact-dependent growth regulation^[2][5]. Dysregulated YAP/TAZ-TEAD signaling promotes tumorigenesis, metastatic progression, and therapy resistance across multiple cancer types, including malignant mesothelioma, non-small cell lung cancer, pancreatic ductal adenocarcinoma, and colorectal cancer^[6][4][7]. In disease models, genetic alterations affecting Hippo pathway components, such as NF2 deficiency, result in aberrant YAP/TAZ-TEAD activation and create dependencies that can be therapeutically exploited through pathway inhibition^[4]. Compared with related transcriptional regulators, TEAD proteins function as the major DNA-binding partners that mediate most YAP/TAZ-driven transcriptional outputs, making TEAD a particularly attractive intervention point for experimental and therapeutic studies^[1][4][8]. For research applications, pharmacological and genetic inhibitors that disrupt YAP/TAZ-TEAD interactions have demonstrated suppression of TEAD-dependent transcription and tumor growth in preclinical models, supporting their use as tools for mechanistic studies and target validation^[4][9].