NUMB and cancer: However, it has been suggested that different subtypes of Numb have different roles in tumors, with NUMB exon 12 (E12) hop isomer p65/p66 promoting epithelial-to-mesenchymal transformation (EMT) and cancer cell migration in vitro and promoting cancer metastasis in mice; the p71/p72 isomer acts as a negative regulator of Notch-1 by ubiquitinating the Notch-1 intracellular domain (N1ICD) and promoting its degradation, and the NUMB isoform is considered to be a key regulator of EMT and cancer cell migration (15).