Inputs include increased mechanical compression, interstitial pressure, inflammation, and MMP-induced ECM remodeling and stiffening from the aberrant microenvironment, giving rise to YAP/TAZ overactivity in cancerous cells, which further stiffens ECM and promotes tumor angiogenesis and invasion by cancer-associated fibroblasts (CAFs), thereby forming a positive-feedback loop that eventuates in melanoma (Figure 4) [43]. The gene discussed is YAP1; the disease is neoplasm.