title: Activation of uPAR is required for cigarette smoke extract-induced epithelial-mesenchymal transition in lung epithelial cells.
abstract: Cigarette smoke is a major risk factor for lung cancer, which may contribute to lung cancer invasion and metastasis. However, the mechanism remains unclear. Epithelial-mesenchymal transition (EMT) is a critical phenotypic alteration of cells that triggers invasion and metastasis. The urokinase-type plasminogen activator receptor (uPAR) is originally thought to assist the directional invasion of migrating cells, and increasing evidences show that overexpression of uPAR in cancer cells promotes EMT. Therefore, we intend to study the role of uPAR in cigarette smoke extract (CSE)-induced EMT in lung epithelial cells. In this study, we showed that lung epithelial cells cultured after CSE treatment demonstrated changes consistent with EMT. E-cadherin was decreased, while vimentin, N-cadherin, and α-SMA expression was increased in both A549 and BEAS-2B cells. Cells acquired a mesenchymal-like morphology and increased cell motility and invasion. In addition, CSE-induced EMT was accompanied by increased expression of uPAR and activation of AKT downstream of uPAR. CSE-induced EMT and activation of AKT were blocked by uPAR gene silencing. Antagonizing PI3K also inhibits development of CSE-induced EMT. We conclude that CSE can induce EMT, and the activity of uPAR-dependent signal pathway in EMT is recapitulated in lung epithelial cells in vitro.
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital, Shandong University, Jinan, P.R. China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Hongchao
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuke
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator; D012906:Smoke; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt