title: ROBO3 promotes growth and metastasis of pancreatic carcinoma.
abstract: Pancreatic carcinoma is a highly lethal malignancy with an extremely poor prognosis. Recent genome-wide studies have implicated axon guidance pathways, including the SLIT/ROBO pathway, in pancreatic tumor development and progression. Here we showed that ROBO3 expression is up-regulated in pancreatic cancer tissue samples and cell lines. Over-expression of ROBO3 promotes pancreatic cancer cell growth, invasion and metastasis in vitro and in mouse xenograft tumor models. We identified miR-383 as a suppressor of ROBO3, and revealed its expression to be inversely correlated with ROBO3. Over-expression of ROBO3 activates Wnt pathway components, β-catenin and GSK-3, and the expression of markers indicating an EMT. By means of immunoprecipitation, we revealed an interaction between Wnt inhibitor SFRP and ROBO3 in pancreatic cancer cell lines. Our work suggests that ROBO3 may contribute to the progression of pancreatic cancer by sequestering Wnt inhibitor SFRP, which in turn leads to increased Wnt/β-catenin pathway activity. We also confirmed that ROBO3 increases with clinical grade and miR-383 expression is inversely correlated to that of ROBO3.
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Medical Intervention Engineering, Tongji University, Shanghai 200072, China.
authors.forename: Shilong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Medical Intervention Engineering, Tongji University, Shanghai 200072, China.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Jichong
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Medical Intervention Engineering, Tongji University, Shanghai 200072, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Medical Intervention Engineering, Tongji University, Shanghai 200072, China. Electronic address: zxpkxy@126.com.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Interventional & Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Institute of Medical Intervention Engineering, Tongji University, Shanghai 200072, China. Electronic address: cjr.limaoquan@163.vip.com.
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D060449:Wnt Signaling Pathway; D000097905:Roundabout Proteins
chemical_list: D035683:MicroRNAs; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C577009:MIRN383 microRNA, mouse; C499630:ROBO3 protein, human; D000097905:Roundabout Proteins
keywords: Invasion; Metastasis; Pancreatic cancer; ROBO3; miR-383