13 Acidic extracellular pH induces the expression of EMT regulator, including ZEB1, Twist1 and Twist2, accompanied with enhancing cell motility and invasion in lung carcinoma.14 Meaningfully, our previous work reveals that acidic microenvironment induces EMT of pancreatic cancer cells through regulating miR-652/ZEB1 pathway.15 In this study, we work to investigate how the acidic extracellular pH, a chemical signaling of metabolic microenvironment, is detected by pancreatic cancer cells and further promotes the transduction of EMT as biological signaling. This evidence concerns the gene TWIST2 and familial pancreatic carcinoma.