The AMPK inactivation promoted the invasion and migration of pancreatic cancer cells in an HSF1‐dependent manner; the metformin‐mediated AMPK activation suppressed the activity of HSF1 and, thus, inhibited the EMT process, suppressed the desmoplastic reaction, and alleviated the inflammatory microenvironment. The gene discussed is HSF1; the disease is familial pancreatic carcinoma.