Fig. 2.

The Notch signaling pathway and its roles in cancer metastasis. The Notch receptors are activated by the Delta-like and Jagged families of ligands expressed on adjacent cells. Upon γ-secretase-mediated proteolysis, NICD proteins translocate to the nucleus and bind to the DNA binding protein CSL, taking the place of the corepressors (CoRs). NICD forms a complex with the DNA binding protein CSL and coactivators (CoAs), leading to the transcriptional activation of Notch target genes. The activation of Notch signaling in tumor microenvironment could promote epithelial-mesenchymal transition (EMT), the anoikis-resistance of tumor cells and maintain the homeostasis of angiogenesis, the morphology of vasculatures and the self-renewal of cancer stem cells (CSCs). Reprinted from Hu et al. [54] with permission from Springer.