YAP1 enhances mesenchymal-type gene expression in human adrenergic-type neuroblastoma cells

High-risk neuroblastoma is a devastating pediatric cancer, with metastasis and relapse being major drivers of mortality. Currently multimodal therapies do not achieve acceptable rates of success in recurrent disease. Phenotypic plasticity between mesenchymal and adrenergic cells has previously been reported. YAP1 is a marker of the mesenchymal-type neuroblastoma cells. MES cells have been shown to be enriched in relapse are hypothesized to contribute to poor patient outcomes. Increased YAP1 expression has been reported in metastatic subpopulations of neuroblastoma cells. To investigate the role of YAP1 in neuroblastoma, we deployed a Tet-ON in-vitro system containing a constitutively activated YAP1S127A. RNA sequencing indicated significant upregulation of MES-type genes upon enforced YAP1 activity and increased resistance towards chemotherapy. Our results indicate a potential role of YAP1 to induce plasticity towards MES-type cells in neuroblastoma, hereby contributing to relapse and therapy resistance. Deepening our understanding of the mechanistic underpinnings enabling neuroblastoma plasticity can contribute to tailoring specific therapies to prevent relapse and therapy resistance.