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Tumor Biology
Published in: Tumor Biology 11/2015

01-11-2015 | Research Article

Robo1 promotes angiogenesis in hepatocellular carcinoma through the Rho family of guanosine triphosphatases’ signaling pathway

Authors: Jian-Yang Ao, Zong-Tao Chai, Yuan-Yuan Zhang, Xiao-Dong Zhu, Ling-Qun Kong, Ning Zhang, Bo-Gen Ye, Hao Cai, Dong-mei Gao, Hui-Chuan Sun

Published in: Tumor Biology | Issue 11/2015

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Abstract

Robo1 is a member of the Robo immunoglobulin superfamily of proteins, and it plays an important role in angiogenesis and cancer. In this study, we investigate the role of roundabout 1 (Robo1) in tumor angiogenesis in hepatocellular carcinoma (HCC). Firstly, the relationship between Robo1 expression on tumors and patient’s survival and endothelial cells in tumor blood vessels and patient’s survival was studied. Secondly, Robo1 was overexpressed or knocked down in human umbilical vein endothelial cells (HUVECs). Cell proliferation, motility, and tube formation were compared in HUVEC with different Robo1 expression. Also, HUVECs with different Robo1 expression were mixed with HCCLM3 and HepG2 hepatoma cells and then implanted in a nude mouse model to examine the effects of Robo1 in endothelial cells on tumor growth and angiogenesis. Cell motility-related molecules were studied to investigate the potential mechanism how Robo1 promoted tumor angiogenesis in HCC. The disease-free survival of the patients with high Robo1 expression in tumoral endothelial cells was significantly shorter than that of those with low expression (P = 0.021). Overexpression of Robo1 in HUVECs resulted in increased proliferation, motility, and tube formation in vitro. In the implanted mixture of tumor cells and HUVECs with an increased Robo1 expression, tumor growth and microvessel density were enhanced compared with controls. Robo1 promoted cell division cycle 42 (Cdc42) expression in HUVECs, and a distorted actin cytoskeleton in HUVECs was observed when Robo1 expression was suppressed. In conclusion, Robo1 promoted angiogenesis in HCC mediated by Cdc42.
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Metadata
Title
Robo1 promotes angiogenesis in hepatocellular carcinoma through the Rho family of guanosine triphosphatases’ signaling pathway
Authors
Jian-Yang Ao
Zong-Tao Chai
Yuan-Yuan Zhang
Xiao-Dong Zhu
Ling-Qun Kong
Ning Zhang
Bo-Gen Ye
Hao Cai
Dong-mei Gao
Hui-Chuan Sun
Publication date
01-11-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 11/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3601-1

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