title: XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells.
abstract: Cigarette smoking contributes to the pathogenesis of chronic obstructive pulmonary disease and lung cancer. Nicotine-derived nitrosamine ketone (NNK) is the most potent carcinogen among cigarette smoking components, and is known to enhance migration of cancer cells. However, the effect of NNK on normal human bronchial epithelial cells is not well studied. XB130 is a member of actin filament associated protein family and is involved in cell morphology changes, cytoskeletal rearrangement and outgrowth formation, as well as cell migration. We hypothesized that XB130 mediates NNK-induced migration of normal human bronchial epithelial cells. Our results showed that, after NNK stimulation, XB130 was translocated to the cell periphery and enriched in cell motility-associated structures, such as lamellipodia, in normal human bronchial epithelial BEAS2B cells. Moreover, overexpression of XB130 significantly enhanced NNK-induced migration, which requires both the N- and C-termini of XB130. Overexpression of XB130 enhanced NNK-induced protein tyrosine phosphorylation and promoted matrix metalloproteinase-14 translocation to cell motility-associated cellular structures after NNK stimulation. XB130-mediated NNK-induced cell migration may contribute to airway epithelial repair; however, it may also be involved in cigarette smoking-related chronic obstructive pulmonary disease and lung cancer.
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto General Research Institute, Toronto, Ontario, Canada.|Department of Thoracic Surgery, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto General Research Institute, Toronto, Ontario, Canada.
authors.forename: Jeya
authors.initials: J
authors.lastname: Nadesalingam
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto General Research Institute, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Serisha
authors.initials: S
authors.lastname: Moodley
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto General Research Institute, Toronto, Ontario, Canada.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Bai
authors.affiliation: Latner Thoracic Surgery Research Laboratories, University Health Network, Toronto General Research Institute, Toronto, Ontario, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.|Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D009602:Nitrosamines / Q000633:toxicity*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014162:Transfection
chemical_list: C521126:AFAP1L2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: F-actin association; airway epithelial cell migration; cortactin; intracellular signal transduction