Schematic representation of nicotine signal transduction pathways. Nicotine activates α7-nAChRs, triggering an initial cytosolic influx of Ca2+, which activates two major signaling pathways (PI3/Akt and MAPK cascade, respectively) resulting in the promotion of cell proliferation, survival and migration. The activation of MAPK and Akt increases NO synthesis, which also promotes EC proliferation, survival and migration. Nicotine causes disassembly of the VE-Cadherin/ β-catenin complex and translocation of β-catenin to the nucleus. By contrast, nicotine binding to α9 opposes this signaling pathway through an unknown mechanism.