Specifically, nicotine activated the PI3K/AKT signaling through the alpha 7 nAChR to inhibit FOXO1 activity and downregulate OTUD3 expression, leading to inhibition of VEGF-C mRNA decay and increase of VEGF-C paracrine secretion in esophageal cancer cells. The gene discussed is FOXO1; the disease is esophageal cancer.