%0 Journal Article
%T The Efficiency of Verteporfin as a Therapeutic Option in Pre-Clinical Models of Melanoma
%A Deborah Lang
%A Elizabeth C. Little
%A Jason W. Lui
%A Jon E. Hammarstedt
%A Kelsey Ogomori
%A Sixia Xiao
%J Journal of Cancer
%D 2019
%I Ivyspring International Publisher
%R 10.7150/jca.27472
%X Yes Associated Protein 1 (YAP) and Transcriptional coactivator with PDZ-Binding Motif (TAZ) have gained notoriety for their ability to drive tumor initiation and progression in a wide variety of cancers, including melanoma. YAP and TAZ act as drivers of melanoma through its interaction with the TEAD family of transcription factors. Verteporfin is a benzoporphyrin derivative that is used clinically for photodynamic treatment of macular degeneration. Recently it has emerged as a potential inhibitor of YAP/TAZ-TEAD interaction independent of light activation. In this study we determine if verteporfin has clinical potential by testing this compound on human melanoma cell cultures and in a clinically significant mouse model, BrafCA; Tyr-CreERT2; Ptenf/f, which parallels human melanoma in terms of disease progression, genetics, and histopathology. In culture, Verteporfin treatment induces a rapid drop in YAP and TAZ protein levels and cell numbers. In the transgenic model, utilizing drug levels that correspond to previously determined safe doses in human patients and with a dosing regimen calculated in this study, Verteporfin did not inhibit melanoma initiation or progression in comparison to mock treated controls. Taken together, our study suggests that although Verteporfin induces YAP/TAZ degradation in melanoma cell lines, Verteporfin was not effective as a YAP/TAZ-TEAD specific inhibitor of melanoma in our studies that aimed to mimic conditions found in clinic in terms of treatment regimen and disease model.
%K melanoma
%K YAP
%K TAZ
%K Verteporfin
%K hippo pathway
%K mouse models
%U http://www.jcancer.org/v10p0001.htm