A Wnt-BMP4 signalling axis induces MSX and NOTCH proteins and promotes growth suppression and differentiation in neuroblastoma

摘要: ABSTRACT The Wnt and bone morphogenetic protein (BMP) signalling pathways are known to be crucial in the development of neural crest lineages, including sympathetic nervous system. Surprisingly, their role paediatric neuroblastoma, prototypic tumour arising from this lineage, remains relatively uncharacterised. We previously demonstrated that Wnt/β-catenin can have cell-type specific effects on neuroblastoma phenotypes, growth inhibition differentiation, BMP4 mRNA were induced by Wnt3a/Rspo2. In study, we characterise phenotypic cells, demonstrating convergent induction MSX homeobox transcription factors BMP4-induced suppression differentiation. Immunohistochemical analysis expression primary neuroblastomas confirms a striking absence poorly differentiated tumours, contrast high ganglion cells. These results consistent with suppressive for neuroblastoma. RNA sequencing following treatment revealed Notch signalling, verified increases Notch3 Hes1 proteins. Together, our data demonstrate first time Wnt-BMP-Notch crosstalk associated