Notch signaling pathway networks in cancer metastasis: a new target for cancer therapy

Notch signaling pathway is evolutionarily conserved in mammals, which plays an important role in cell development and differentiation. In recent years, increasing evidence has shown that aberrant activation of Notch is associated with tumor process. Aberrant activation of Notch signaling pathway has been found in many different solid tumors can induce cell proliferation, metastasis and epithelial-mesenchymal transition. Notch receptor and its ligand are both single transmembrane protein, and Notch is activated when it binds to the Notch ligand of neighbor cells. The signal transduction of Notch signaling pathway is only between cells that are in contact with each other, which is independent of second messengers. Thus, Notch needs to cross talk with other signaling pathways, including PI3K/AKT, NF-κB, integrin and miRNAs, to precisely regulate cell fate. In this review, we summarize the roles of Notch signaling pathway in tumor metastasis and its regulatory mechanisms and discuss the current treatment strategies targeting Notch signal pathway.