Developmental pathways associated with cancer metastasis: Notch, Wnt, and Hedgehog

Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death,motility, migration, and stemness. These systems are not only commonly activated in many solid tumors, where they drive orcontribute to cancer initiation, but also in primary and metastatic tumor development. The reactivation of developmentalpathways in cancer stroma favors the development of cancer stem cells and allows their maintenance, indicating these signalingpathways as particularly attractive targets for efficient anticancer therapies, especially in advanced primary tumors and metastaticcancers. Metastasis is the worst feature of cancer development. This feature results from a cascade of events emerging from thehijacking of epithelial-mesenchymal transition, angiogenesis, migration, and invasion by transforming cells and is associated withpoor survival, drug resistance, and tumor relapse. In the present review, we summarize and discuss experimental data suggestingpivotal roles for developmental pathways in cancer development and metastasis, considering the therapeutic potential. Emergingtargeted antimetastatic therapies based on Notch, Wnt, and Hedgehog pathways are also discussed.