Upregulation of the chromatin remodeler HELLS is mediated by YAP1 in Sonic Hedgehog Medulloblastoma.

摘要: Medulloblastoma is a malignant pediatric tumor that arises from neural progenitors in the cerebellum. Despite five-year survival rate of ~70%, nearly all patients incur adverse side effects current treatment strategies drastically impact quality life. Roughly one-third medulloblastoma are driven by aberrant activation Sonic Hedgehog (SHH) signaling pathway. However, scarcity genetic mutations has led to investigation other mechanisms contributing cancer pathogenicity including epigenetic regulation gene expression. Here, we show Helicase, Lymphoid Specific (HELLS), chromatin remodeler with functions DNA methylation and histone modification, induced SHH-dependent cerebellar progenitor cells developing murine cerebella. HELLS also up-regulated mouse human SHH medulloblastoma. Others have shown activity generally results repressive state. Our demonstrate increased expression our experimental systems regulated oncogenic transcriptional regulator YAP1 downstream Smoothened, positive transducer signaling. Elucidation as one effectors pathway may lead novel targets for precision therapeutics promise better outcomes patients.