Abstract
Hippo was first identified in a genetic screen as a protein that suppressed proliferation and cell growth. Subsequently, it was shown that hippo acted in a so-called canonical cascade to suppress Yorkie, the Drosophila equivalent of Yes-activated protein (YAP), a mechanosensitive transcriptional cofactor that enhances the activity of the TEAD family of transcription factors. YAP promotes fibrosis, activation of cancer-associated fibroblasts, angiogenesis and cancer cell invasion. YAP activates the expression of the matricellular proteins CCN1 (cyr61) and CCN2 (ctgf), themselves mediators of fibrogenesis and oncogenesis, and coordination of matrix deposition and angiogenesis. This review discusses how therapeutically targeting YAP through YAP inhibitors verteporfin and celastrol and its downstream mediators CCN1 and CCN2 might be useful in treating melanoma.