XB130 translocation to microfilamentous structures mediates NNK-induced migration of human bronchial epithelial cells.

Qifei Wu,Jeya Nadesalingam,Mingyao Liu,Xiaohui Bai,Serisha Moodley

doi:10.18632/oncotarget.3777

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.

Highlights

Chronic obstructive pulmonary disease (COPD) affects over 300 million people worldwide, it was ranked as the third-leading cause of death, killing over 3 million people each year [1]
After nitrosamine ketone (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
NNK treatment resulted in tyrosine phosphorylation of XB130 and interaction of XB130 with cortactin, which may be responsible for the translocation of XB130 to the cytoskeleton

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) affects over 300 million people worldwide, it was ranked as the third-leading cause of death, killing over 3 million people each year [1]. Cigarette smoking is the most common causes of COPD [3], and it is a risk factor of lung cancer. Nicotine-derived nitrosamine ketone (NNK), known as 4-(methylnitrosamino)-1-(3-pyridyl)-1butanone, is a nicotine-derived cigarette smoke component and a potent tobacco-specific carcinogen [4,5,6]. NNK accounts for approximately 27% of the end products formed in tobacco smoke, and it has been shown to be the most potent systemic lung carcinogen in rodents [7]. Treatment of normal human airway epithelial cells with NNK promoted cell transformation www.impactjournals.com/oncotarget by decreasing cellular dependence on extracellular growth factor stimulation, contact inhibition, and adherence to extracellular matrix [5, 10]. Understanding the effects and underlying mechanisms of NNK on normal bronchial epithelial cells is important for preventing COPD, lung cancer and other respiratory diseases

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