A Wnt-BMP4 Signaling Axis Induces MSX and NOTCH Proteins and Promotes Growth Suppression and Differentiation in Neuroblastoma.

作者: Marianna Szemes , Zsombor Melegh , Jacob Bellamy , Alexander Greenhough , Madhu Kollareddy

DOI: 10.3390/CELLS9030783

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摘要: The Wnt and bone morphogenetic protein (BMP) signaling pathways are known to be crucial in the development of neural crest lineages, including sympathetic nervous system. Surprisingly, their role paediatric neuroblastoma, prototypic tumor 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 characterised phenotypic cells, demonstrating convergent induction MSX homeobox transcription factors BMP4-induced suppression differentiation. An immunohistochemical analysis expression primary neuroblastomas confirms a striking absence poorly differentiated tumors, contrast high ganglion cells. These results consistent with suppressive for neuroblastoma. RNA sequencing following treatment revealed Notch signaling, verified increases Notch3 Hes1 proteins. Together, our data demonstrate, first time, Wnt-BMP-Notch crosstalk associated

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