Evidence of this has been observed in colorectal cancer with upregulation of NOTCH1, JAG ligands, and HES1 resulting in increases in EMT stemness proteins (CD44, SLUG, and SMAD3).59,60 There is a need to study how the Notch pathway may drive dedifferentiation of SCs and stemness leading to MPNSTs in NF1 patients. This evidence concerns the gene SMAD3 and colorectal cancer.