title: Effects of Slit3 silencing on the invasive ability of lung carcinoma A549 cells.
abstract: Slit proteins function as chemorepellents in axon guidance and neuronal migration by binding to cognate Robo receptors. The Slit/Robo signaling pathway is also involved in the regulation of tumor cell metastasis. However, whether the Slit/Robo signaling pathway exerts prometastatic or antimetastasis functions remains controversial. To date, most of the research on Slit/Robo has focused on Slit2, and the effects of Slit3 on metastasis remain largely unknown. Based on the Oncomine database, overall expression of Slit3 is low in tumor tissues compared to its level in normal tissues. The underlying mechanism for slit3 silencing in tumor tissues is likely related to hypermethylation of the slit3 promoter. However, lung carcinomas appear to be an exception. Several studies have reported that the frequency of Slit3 methylation in lung cancers is far lower than the frequency of Slit2. In the present study, high Slit3 expression at the mRNA level, yet not at the protein level, was detected in lung adenocarcinoma A549 cells. The function of Slit3 in tumor migration and invasion was examined by silencing of Slit3 expression in A549 cells. Silencing of Slit3 promoted proliferation, migration and invasion of A549 cells and induced epithelial-mesenchymal transition by downregulation of E-cadherin and upregulation of vimentin. The inhibitory effects of Slit3 on tumor migration and invasion are likely related to matrix metalloproteinases (MMPs). Silencing of Slit3 in the A549 cells enhanced MMP2 and MMP9 expression. These results indicate that Slit3 is a potential tumor suppressor in lung adenocarcinoma.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Chengzhi
authors.initials: C
authors.lastname: Sui
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Xianyuan
authors.initials: X
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Liying
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Fu'an
authors.initials: F
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness
chemical_list: D008565:Membrane Proteins; C498990:SLIT3 protein, human