Figure 5.

Plasticity from a noradrenergic to a mesenchymal identity in neuroblastoma defines a NOR-to-MES transition (NMT) reminiscent of the epithelial-to-mesenchymal transition (EMT). EMT, controlled by EMT effectors (SNAI1/2, ZEB1/2, TWIST1/2), refers to a shift from an epithelial cell expressing the emblematic marker E-cadherin to a cell expressing various mesenchymal markers. MET is known to be the reversion of EMT. NMT refers to the mechanism by which NOR cells transdifferentiate toward MES cells. Neuroblastoma NOR cells express typical neurofilament proteins and chromogranins as well as TH and DBH. MES neuroblastoma cells exhibit expression of typical mesenchymal markers such as vimentin and fibronectin. PRRX1 or NOTCH3-IC over-expression, as well as knock-out of GATA3 or ARID1A, have been shown to be able to induce NMT. The reverse mechanism is thus called MNT.