title: Slit2‑Robo1 signaling promotes the adhesion, invasion and migration of tongue carcinoma cells via upregulating matrix metalloproteinases 2 and 9, and downregulating E‑cadherin.
abstract: Whether Slit homologue 2 (Slit2) inhibits or promotes tumor cell migration remains controversial, and the role of Slit2‑Roundabout 1 (Robo1) signaling in oral cancer remains to be fully elucidated. The aim of the present study was to investigate the role of Slit2‑Robo1 signaling in the adhesion, invasion and migration of tongue carcinoma cells, and the mechanism by which Slit2‑Robo1 signaling inhibits or promotes tumor cell migration. Tca8113 tongue carcinoma cells were treated with the monoclonal anti‑human Robo1 antibody, R5, to inhibit the Slit2‑Robo1 signaling pathway, with immunoglobulin (Ig)G2b treatment as a negative control. The expression levels of Slit2 and Robo1 were determined using flow cytometry. The effects of R5 on the adhesion, invasion and migration of Tca8113 tongue carcinoma cells were investigated. Gelatin zymography was used to investigate the activity of matrix metalloproteinase 2 (MMP2) and MMP9. Western blot analysis was used to evaluate the expression levels of E‑cadherin in Tca8113 cells treated with 10 µg/ml of either R5 or IgG2b. Slit2 and Robo1 proteins were found to be expressed in the Tca8113 cells. R5 significantly inhibited the adhesion, invasion and migration of Tca8113 cells in vitro. R5 also inhibited the activities of MMP2 and MMP9, and increased the expression of E‑cadherin in the Tca8113 cells. These results suggested that Slit2‑Robo1 signaling promoted the adhesion, invasion and migration of tongue carcinoma cells by upregulating the expression levels of MMP2 and MMP9 and, downregulating the expression of E‑cadherin.
authors.affiliation: Department of Oral Basic Science, College of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510620, P.R. China.
authors.forename: Feng-Li
authors.initials: FL
authors.lastname: Zhou
authors.affiliation: Department of Urology, Lanzhou General Hospital of Military Region, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Li
authors.affiliation: Department of Oral Basic Science, College of Stomatology, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D015398:Signal Transduction; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D015820:Cadherins; D036341:Intercellular Signaling Peptides and Proteins; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein