Wu Qifei, Nadesalingam Jeya, Moodley Serisha, Bai Xiaohui, Liu Mingyao
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.
Oncotarget. 2015 Jul 20;6(20):18050-65. doi: 10.18632/oncotarget.3777.
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.
吸烟会导致慢性阻塞性肺疾病和肺癌的发病。尼古丁衍生的亚硝胺酮（NNK）是香烟成分中最具致癌性的物质，已知它会增强癌细胞的迁移能力。然而，NNK对正常人支气管上皮细胞的影响尚未得到充分研究。XB130是肌动蛋白丝相关蛋白家族的成员，参与细胞形态变化、细胞骨架重排和突起形成，以及细胞迁移。我们假设XB130介导NNK诱导的正常人支气管上皮细胞迁移。我们的结果表明，在NNK刺激后，XB130转位到细胞周边，并在正常人支气管上皮BEAS2B细胞的细胞运动相关结构（如片状伪足）中富集。此外，XB130的过表达显著增强了NNK诱导的迁移，这需要XB130的N端和C端。XB130的过表达增强了NNK诱导的蛋白酪氨酸磷酸化，并促进了NNK刺激后基质金属蛋白酶-14向细胞运动相关细胞结构的转位。XB130介导的NNK诱导的细胞迁移可能有助于气道上皮修复；然而，它也可能与吸烟相关的慢性阻塞性肺疾病和肺癌有关。
