It is reported that Rap1 can modulate the activation of the ERK/MAP kinase pathway via B-Raf to regulate the cell–matrix adhesion and cell–cell junctions by activating integrins via RAPL and RIAM. The available data indicate that Rap1b expression is aberrantly altered in various cancer-related diseases and involved in the pathogenesis of cancers, including human colorectal carcinoma,Compound Library esophageal squamous cell carcinoma, squamous carcinomas, and ovarian cancer. In terms of gastric cancer, Rap1b was recently identified to be highly expressed and is significantly associated with malignant behavior and poor prognosis in gastric cancer. However, the specific role and potential mechanism of Rap1b in human gastric cancer tumorigenesis and cancer cells motility are not clear. Autophagy and apoptosis, two different types of programmed cell death, occur in multicellular organisms and have important roles in maintaining metabolic homeostasis. By “self-eating” or self-killing,FDA-approved Compound Library autophagy and apoptosis caused by stress can degrade the damaged protein and organelles to make damaged cells survive or program death. The dysfunction of autophagy and apoptosis has severe pathophysiological consequences and is significantly associated with tumor angiogenesis (9–11). In the present study, we aimed to determine the expression of Rap1b in human gastric cancer tissues and cells. Furthermore, we addressed whether and how Rap1b affects the autophagy and apoptosis of gastric cancer cells in vitro. We also investigated the interaction between Rap1b and the PI3K/Akt/mTOR pathway to further elucidate the potential role of Rap1b in gastric cancer. As a member of the small GTPase Ras family, Rap1b has been demonstrated to be aberrantly expressed and involved in the development of several cancers. In colorectal carcinoma, Rap was found to be directly targeted by miR-100 and miR-139 and overexpressed in cancer tissues, contributing to the proliferation and invasion of human colorectal cancer cells. Highly expressed Rap1b is also associated with the enhanced proliferation and invasion as well as repressed apoptosis in esophageal squamous cell carcinoma, which is inhibited by miR-518b.