title: Slit2/Robo1 signaling promotes intestinal tumorigenesis through Src-mediated activation of the Wnt/β-catenin pathway.
abstract: Slit2 is often overexpressed in cancers. Slit2 is a secreted protein that binds to Roundabout (Robo) receptors to regulate cell growth and migration. Here, we employed several complementary mouse models of intestinal cancers, including the Slit2 transgenic mice, the ApcMin/+ spontaneous intestinal adenoma mouse model, and the DMH/DSS-induced colorectal carcinoma model to clarify function of Slit2/Robo1 signaling in intestinal tumorigenesis. We showed that Slit2 and Robo1 are overexpressed in intestinal tumors and may contribute to tumor generation. The Slit2/Robo1 signaling can induce precancerous lesions of the intestine and tumor progression. Ectopic expression of Slit2 activated Slit2/Robo1 signaling and promoted tumorigenesis and tumor growth. This was mediated in part through activation of the Src signaling, which then down-regulated E-cadherin, thereby activating Wnt/β-catenin signaling. Thus, Slit2/Robo1 signaling is oncogenic in intestinal tumorigenesis.
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zhang
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Da-Lei
authors.initials: DL
authors.lastname: Zhou
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Sheng-Xia
authors.initials: SX
authors.lastname: Chen
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hong-Ju
authors.initials: HJ
authors.lastname: Gou
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Qu-Liang
authors.initials: QL
authors.lastname: Gu
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: He
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Cui-Ling
authors.initials: CL
authors.lastname: Qi
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Jiang-Chao
authors.initials: JC
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Ding
authors.affiliation: Storr Liver Center, Westmead Millennium Institute for Medical Research, The Western Clinical School of the Faculty of Medicine, The University of Sydney at the Westmead Hospital, Westmead, NSW, Australia.
authors.forename: Liang
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D000236:Adenoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D017491:Genes, APC; D045325:HCT116 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D047368:Tumor Burden; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D051176:beta Catenin; D019061:src-Family Kinases; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse