Multiple evidence indicates that tumor-initiating cells depend on the same signaling pathways that regulate normal ISC function including Notch [12,13,14,15,16,17,18], Wnt//β-catenin [19,20] and TGF-β [21], through activation of a stem cell transcriptional program containing genes such as Lgr5, Bmi1, EphB2 or Hes1. This evidence concerns the gene EPHB2 and neoplasm.