Recently, Ulasov et al. found that Temozolomide (TMZ) facilitates nuclear translocation of MMP14, followed by extracellular release of canonical Notch1 and Notch3 ligand Dll4, which in turn promotes cleavage of Notch3 and its nuclear translocation and induces glioma sphering ability and stemness (Ulasov et al., 2020). Here, DLL4 is linked to central nervous system cancer.