Overexpression of Rab11-FIP2 in colorectal cancer cells promotes tumor migration and angiogenesis through increasing secretion of PAI-1

Wenjie Dong,Xinai Wu

doi:10.1186/s12935-018-0532-0

Abstract

BackgroundRab11 family-interacting protein 2 (Rab11-FIP2) can interact with MYO5B and plays an important role in regulating plasma membrane recycling. However, little is known about the clinical significance of DUSP2 in colorectal cancer (CRC).MethodsIn this study, we investigated Rab11-FIP2 expression by immunohistochemistry in 125 patients with colorectal cancer. Conditioned media containing all secreted factors was harvested. Chemokine secretion and expression were analyzed by Chemi-array.ResultsWe found that the expression level of Rab11-FIP2 was significantly increased in colorectal cancer tissues and high expression of Rab11-FIP2 was closely correlated with nodal metastasis in colorectal cancer patients. Rab11-FIP2 overexpression promoted colorectal cancer metastasis in vitro and in vivo. Finally, we demonstrated that Rab11-FIP2 overexpression may contribute to increased secretion of PAI-1 in human colorectal cancer cells.ConclusionsOur findings reveal a novel mechanism underlying the role of Rab11-FIP2 in colorectal cancer dissemination, suggesting that targeting Rab11-FIP2 might be a promising therapeutic strategy for CRC.

Highlights

Rab11 family-interacting protein 2 (Rab11-FIP2) can interact with MYO5B and plays an important role in regulating plasma membrane recycling
It was reported that Rab11-FIP2 regulated CXCR2 recycling and receptor-mediated chemotaxis and that passage of internalized CXCR2 through Rab11a-positive recycling system is critical for physiological response to a chemokine, suggesting that Rab11-FIP2 may play a role in chemotaxis [6]
We showed that Rab11-FIP2 overexpression may contribute to increased secretion of PAI-1 in human colorectal cancer cells

Summary

Introduction

Rab family-interacting protein 2 (Rab11-FIP2) can interact with MYO5B and plays an important role in regulating plasma membrane recycling. Growing evidence demonstrates that Rab11-FIP2 plays a substantial regulatory role in tumor progression and metastasis. It was reported that Rab11-FIP2 regulated CXCR2 recycling and receptor-mediated chemotaxis and that passage of internalized CXCR2 through Rab11a-positive recycling system is critical for physiological response to a chemokine, suggesting that Rab11-FIP2 may play a role in chemotaxis [6]. PAI-1 and IL-8 were identified to be correlated with tumor grade/stage and prognosis [7,8,9]. PAI-1 and IL-8 were identified to be correlated with tumor angiogenesis [10]. We showed that Rab11-FIP2 overexpression may contribute to increased secretion of PAI-1 in human colorectal cancer cells.

Methods

Results

Conclusion