Helicobacter pylori infection can lead to epithelial-to-mesenchymal transition (EMT) and the progression of gastric cancer (GC); however, the underlying mechanism is poorly understood. Lysosomal-associated protein transmembrane 40 (LAPTM4B) has been implicated in carcinogenesis, including in GC, and we previously showed that LAPTM4B-35 overexpression was an independent prognostic factor in GC. In this study, we demonstrate that upregulation of LAPTM4B promotes GES-1 human gastric epithelial cell proliferation, migration, and invasion and EMT. Conversely, LAPTM4B downregulation inhibited proliferation, migration, invasion, and EMT in SGC7901 GC cells. We also found that H. pylori infection enhanced LAPTM4B expression and induced EMT in GES-1 cells. Thus, EMT in GC is promoted by a combination of LAPTM4B overexpression and H. pylori infection. These results provide a basis for the development of novel two-pronged therapeutic strategies for the treatment of GC. (C) 2019 Published by Elsevier Inc.