WWTR1 (TAZ) is a transcriptional coactivator and central effector of the Hippo signaling pathway that regulates organ size and tumor suppression by restraining proliferation and promoting apoptosis. In the canonical Hippo cascade, the kinases STK3/MST2 and STK4/MST1 phosphorylate and activate LATS1/2, which in turn inactivates WWTR1. WWTR1 functions as a mechanotransducer, relaying extracellular matrix stiffness and cell-shape cues through Rho GTPase and actin-myosin tension to control proliferation, stem-cell self-renewal, and epithelial-mesenchymal transition 1. WWTR1 integrates mechanical signals with metabolic pathways and soluble growth cues to regulate transcription through interaction with TEAD family factors 2. In cancer, WWTR1 activation drives oncogenic programs including cancer stem-cell properties, chemoresistance, and metastatic capacity across solid tumors 3. Recent evidence reveals that matrix stiffness sustains cancer stemness through TAZ-mediated phase separation with NANOG, promoting transcription of pluripotency factors 4. WWTR1 dysregulation is implicated in hepatocellular carcinoma, breast cancer, esophageal cancer, and gastric carcinoma. Therapeutic strategies targeting WWTR1 or its downstream effectors offer potential to reduce cancer stem cells and enhance chemosensitivity, though approaches must account for context-dependent pro- and anti-cancer YAP/TAZ activities across tumor types 5.