Background: Glucose-6-phosphate isomerase (GPI) is a glycolytic-related enzyme that interconverts glucose-6-phosphate and fructose-6-phosphate in the cytoplasm. This protein is also secreted into the extracellular matrix by cancer cells and is, therefore, also called autocrine motility factor (AMF). 
Methods: To clarify the roles of AMF/GPI in gastric cancer (GC), we collected 335 GC tissues and the corresponding adjacent noncancerous tissues, performed immunohistochemical studies, and analyzed the relationship between AMF/GPI expression and the patients’ clinicopathologic features. 
Results: AMF/GPI expression was found to be significantly higher in the GC group than in the corresponding noncancerous tissue group (P <0.001). Additionally, AMF/GPI expression positively associated with a higher TNM stage and poorer prognosis in patients. Through Kaplan–Meier analysis and according to the Oncomine database, we found that AMF/GPI was overexpressed in GC tissues compared to normal mucosa, and the patients with higher AMF/GPI expression had poorer outcomes. We used AMF/GPI-silenced GC cell lines to observe how changes in AMP/GPI affect cellular phenotypes. AMF/GPI knockdown suppressed proliferation, migration, invasion, and glycolysis, and induced apoptosis in GC cells. 
Conclusion: These findings suggest that AMF/GPI overexpression is involved in carcinogenesis and promotes the aggressive phenotypes of GC cells.
Keywords: gastric cancer, glucose-6-phosphate isomerase, autocrine motility factor, tumorigenesis, prognosis, metabolism