Rab11‐FIP2 promotes the metastasis of gastric cancer cells

Rab11‐FIP2 can interact with MYO5B and plays an important role in regulating plasma membrane recycling. Our previous study has shown that MYO5B is epigenetically silenced and associated with c‐Met signaling in human gastric cancer. However, little is known of the function of Rab11‐FIP2 in gastric cancer. In this study, we investigated Rab11‐FIP2 expression by immunohistochemistry in 86 patients with gastric cancer. We found that the expression level of Rab11‐FIP2 was significantly increased in gastric cancer tissues and high expression of Rab11‐FIP2 was closely correlated with nodal metastasis in gastric cancer patients. Rab11‐FIP2 overexpression promoted epithelial–mesenchymal transition (EMT) in a manner associated with gastric cancer metastasis in vitro and in vivo. We also found that hypoxia could enhance the expression of Rab11‐FIP2 through HIF‐1α. Inactivation of Rab11‐FIP2 dramatically decreased hypoxia‐induced migration of gastric cancer cells. Suppression of the internalization of EGFR, at least in part, plays an important role in EMT induced by overexpression of Rab11‐FIP2 in gastric cancer cells. Finally, we demonstrated that Rab11‐FIP2 could regulate actin cytoskeleton dynamics. In conclusion, our findings reveal a novel mechanism underlying the role of Rab11‐FIP2 in gastric cancer dissemination, suggesting that Rab11‐FIP2 may be a promising candidate target for gastric cancer treatment.