While the chemical signaling between tumor and the TME occurs via a variety of growth factors, cytokines, chemokines as well as other chemical ligand-receptor systems, the physical signaling occurs via dynamic changes in the ECM stiffness, liquid pressure, and cell density that are sensed by the tumor cells by a variety of mechanoreceptors and sensors, such as integrins and associated signaling molecules like YAP2–4. Here, YAP1 is linked to neoplasm.