N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells
Menée in vitro à l’aide d’un organoïde de prostate, cette étude montre que différents sous-types de cancer de la prostate peuvent se développer à partir de différents types de cellules épithéliales basales et luminales
MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention.