Fig. 6.

Modeling NPY-epithelial cross talk that favors cell survival and proliferation and inhibits apoptosis. NPY released from the enteric neurons can activate phosphatidyl-inositol-3-kinase (PI3-K) pathway and increase pAkt signals leading to cell survival, and proliferation via c-Myc and cyclin D1. In addition, NPY also downregulates miR-375, thereby reducing apoptosis. Furthermore, NPY also inhibits p21, which mediates cell cycle arrest (G1 to the synthetic S phase). Taken together, NPY-induced enhancement in cell survival and proliferation with a concomitant downregulation of apoptosis facilitates inflammation-induced tumorigenesis.