Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 138, Issue 7, Pages 1680-1688Publisher
WILEY-BLACKWELL
DOI: 10.1002/ijc.29899
Keywords
Rab11-FIP2; gastric cancer; hypoxia; HIF-1 alpha; metastasis
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Funding
- National Natural Science Foundation of China [81302120]
- First Affiliated Hospital of Zhengzhou University (Youth Innovation Fund)
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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-1 alpha. 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.
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