NOTCH3 is a master-regulator of motility in neuroblastoma and is essential for cell survival

Migratory embryonal neuroblasts give rise to several tissues, including the sympathetic nervous system (SNS). Neuroblastomas are paediatric tumours of the peripheral SNS with a highly variable prognosis. We observed that high NOTCH3 expression in neuroblastomas correlated with a poor prognosis. Expression of a NOTCH3 transgene in neuroblastoma cells induced many motility genes and conferred a highly motile phenotype. Expression of these motility genes strongly correlated with NOTCH3 expression in neuroblastomas and many other tumours, suggesting a general role for NOTCH3 in regulation of these genes. Silencing of NOTCH3 or genes of the Notch-processing γ-secretase complex induced apoptosis in all neuroblastoma cell lines tested. These data suggest that NOTCH3 is a key-regulator of motility, and indispensable for survival of neuroblastoma cells. Time-course experiments of NOTCH3IC induction in two independent clones (c6 and c8), with 9 or 8 time points, respectively.