title: Robo1 promotes angiogenesis in hepatocellular carcinoma through the Rho family of guanosine triphosphatases' signaling pathway.
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.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.|The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
authors.forename: Jian-Yang
authors.initials: JY
authors.lastname: Ao
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.|Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
authors.forename: Zong-Tao
authors.initials: ZT
authors.lastname: Chai
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Department of Hepatobiliary Surgery, Binzhou Medical College Affiliated Hospital, Binzhou, Shandong, 256610, China.
authors.forename: Ling-Qun
authors.initials: LQ
authors.lastname: Kong
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.
authors.forename: Bo-Gen
authors.initials: BG
authors.lastname: Ye
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China.
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Gao
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China. sun.huichuan@zs-hospital.sh.cn.|Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, China. sun.huichuan@zs-hospital.sh.cn.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D003598:Cytoskeletal Proteins; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D020741:rho GTP-Binding Proteins; D000097905:Roundabout Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D020741:rho GTP-Binding Proteins; D000097905:Roundabout Proteins; C075598:CDC42EP1 protein, human
keywords: Angiogenesis; Hepatocellular carcinoma; Rho GTPase; Roundabout receptors 1