Role of YAP/TAZ downstream of common oncogenic drivers

YAP and TAZ are transcriptional coactivators that play a central role in cancer initiation and growth. Despite being widespread activated in a number of human malignancies, YAP/TAZ aberrant triggering is rarely due to genetic alteration, but it is likely occurring as a consequence of mis-regulation of the complex network of signaling pathways that converge on these factors. We thus asked if recurrent oncogenic lesions, that are considered as tumorigenic drivers, might work though YAP/TAZ to induce cell transformation. We found that YAP/TAZ are not only activated upon oncogenic stimulation, but are required for the onset of malignant phenotypes induced by oncogenes in carcinogenesis models both in vitro and in vivo. Interestingly, we also found that the physical composition of the extracellular environment is crucial to allow oncogenes to foster tumor initiation and progression, by sustaining YAP/TAZ activity. Indeed, cells that are not able to properly organize F-actin cytoskeleton are refractory to oncogene-induced transformation. The finding that YAP/TAZ are the molecular nexus on which different tumorigenic drivers converge, and that oncogenes mediated transformation requires proficient transduction of mechanical signals to YAP/TAZ, might have relevant implications for the identification of a common molecular target to inhibit tumor onset