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.
Department of Internal Medicine-Oncology, the First Affiliated Hospital, Zhengzhou University, China.
Wenjie
W
Dong
Department of Internal Medicine-Oncology, the First Affiliated Hospital, Zhengzhou University, China.
Guohui
G
Qin
Department of Gastroenterology, Rui-Jin Hospital, Shanghai Jiao Tong University, Shanghai, China.
Ruizhe
R
Shen
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000368:Aged; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D046888:Tissue Array Analysis; D020691:rab GTP-Binding Proteins
D002352:Carrier Proteins; D008565:Membrane Proteins; C463963:RAB11FIP2 protein, human; D020691:rab GTP-Binding Proteins
HIF-1α; Rab11-FIP2; gastric cancer; hypoxia; metastasis