Increased YAP and TAZ protein stability, nuclear translocation, and increased transcriptional activation in cancer cells can occur downstream of multiple oncogenic and cellular stress (i.e., mechanical stress, hypoxia) signals, and can be mediated by activated receptor and non-receptor tyrosine kinases, GPCRs, adhesion receptors, and Rho GTPases through Hippo-dependent and -independent pathways (Figure 2). This evidence concerns the gene WWTR1 and cancer.