Verteporfin induced SUMOylation of YAP1 in endometrial cancer.

Yes-associated protein (YAP or YAP1) has been proposed to function as an oncogene in most cancers, with nuclear localization of YAP1 correlating with poor prognosis. Photosensitizer Verteporfin has been proven as an inhibitor of YAP1 through preventing the combination of YAP1 with TEA domain transcription factor (TEAD). We showed previously that the total and phospho-levels of YAP1 were related to the clinical characteristics and outcomes in endometrial cancer (EC) patients, and that YAP1 promoted the proliferation and metastasis of EC cells in vitro cell line studies and in animal models. We also reported that Verteporfin inhibited cell growth and induced cell death through inhibiting YAP1 in EC in our previous study. However, the mechanism of how Verteporfin inhibits the function of YAP1 remains unclear. In this study, we analyzed the global effects of Verteporfin on cell function by using Reverse Phase Protein Arrays (RPPA) and Ingenuity Pathway Analysis (IPA). Furthermore, we demonstrated that Verteporfin induced the SUMOylation of YAP1 for the first time. Interestingly, we found that the SUMOylation of YAP1 was regulated by YAP1 phosphorylation. Together, our study revealed a novel mechanism by which Verteporfin inhibits the function of YAP1 through regulating YAP1 SUMOylation. Our study may provide a rationale for the clinical use of Verteporfin in endometrial cancer by targeting YAP1.