Our study confirmed that overexpression of NLK increased the expression of p-PI3K (Tyr458), p-AKT (Ser473), and p-mTOR (Ser2448) in vitro, while knockout of NLK suppressed the PI3K/AKT/mTOR signaling pathway and inhibited EMT in pancreatic cancer cell lines. The gene discussed is NLK; the disease is familial pancreatic carcinoma.