The Notch-Mediated Proliferation Circuitry.

The essential and highly conserved Notch signaling pathway controls a wide range of cell fate decisions during development, including cellular proliferation. Notch mediates both pro- and anti-proliferative effects in development, stem cells, and cancer depending on cellular context. Furthermore, it can induce proliferation in both cell-autonomous and non-cell-autonomous manners. Interacting genes and crosstalking signaling pathways play essential roles in regulating the proliferative response to Notch signals. A large number of genes that participate in the Notch network to influence proliferation have been identified, including several that activate the JNK signaling pathway, which interacts with Notch to induce both hyperplastic and invasive cellular behaviors. It is clear that dissecting the genetic circuitry surrounding Notch is essential to understanding the proliferative response to Notch in both development and cancer.