Cigarette smoke-induced alveolar epithelial–mesenchymal transition is mediated by Rac1 activation

Shen, Huijuan; Sun, Yanhong; Zhang, Shui-juan; Jiang, Jun; Dong, Xiaopeng; Jia, Yongyi; Shen, Jian; Guan, Yan; Zhang, Linhui; Li, Fenfen; Lin, Xiaofeng; Wu, Ximei; Xie, Qiang-min; Yan, Xiaofeng

doi:10.1016/j.bbagen.2014.01.033

Cited by 60 publications

(47 citation statements)

References 40 publications

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“…It has been reported that Rac activity is required for gelsolininduced epithelial cell invasion 29 and gelsolin-mediated collagen phagocytosis in fibroblasts. 30 In some settings, for example, cigarette smoke-exposed pulmonary epithelial cells, 31 Rac1 inhibition, or knockdown disrupted the activation of Akt. These studies suggest a possibility that Rac signaling may mediate the link between gelsolin and Akt activation.…”

Section: Discussionmentioning

confidence: 99%

Gelsolin Promotes Radioresistance in Non–Small Cell Lung Cancer Cells Through Activation of Phosphoinositide 3-Kinase/Akt Signaling

Zhao

Wang

et al. 2016

Technol Cancer Res Treat

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Gelsolin is an actin-binding protein and acts as an important regulator of cell survival. This study aimed to determine the function of gelsolin in the radioresistance of non-small cell lung cancer cells. We examined the expression of gelsolin in radioresistant A549 and H460 cells and their parental cells. The effects of gelsolin overexpression and knockdown on the clonogenic survival and apoptosis of non-small cell lung cancer cells after irradiation were studied. The involvement of phosphoinositide 3-kinase/Akt signaling in the action of gelsolin was checked. We found that gelsolin was significantly upregulated in radioresistant A549 and H460 cells. Overexpression of gelsolin significantly (P < .05) increased the number of colonies from irradiated A549 and H460 cells compared to transfection of empty vector. In contrast, knockdown of gelsolin significantly (P < .05) suppressed colony formation after irradiation. Gelsolin-overexpressing cells displayed reduced apoptosis in response to irradiation, which was coupled with decreased levels of cleaved caspase-3 and poly adenosine diphosphate-ribose polymerase. Ectopic expression of gelsolin significantly (P < .05) enhanced the phosphorylation of Akt compared to nontransfected cells. Pretreatment with the phosphoinositide 3-kinase inhibitor LY294002 (20 mmol/L) significantly decreased clonogenic survival and enhanced apoptosis in gelsolin-overexpressing A549 and H460 cells after irradiation. Taken together, gelsolin upregulation promotes radioresistance in non-small cell lung cancer cells, at least partially, through activation of phosphoinositide 3-kinase/Akt signaling.

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Section: Discussionmentioning

confidence: 99%

Gelsolin Promotes Radioresistance in Non–Small Cell Lung Cancer Cells Through Activation of Phosphoinositide 3-Kinase/Akt Signaling

Zhao

Wang

et al. 2016

Technol Cancer Res Treat

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“…In line with this, a recent investigation showed that treatment of lung epithelial cells with CS extracts induced alveolar EMT through a cascade of biological mechanisms characterized by a rise in TGF-beta and Rac1/Smad2 signaling pathway (113). Interestingly, the blockade of TGF-beta activity attenuated EMT expression markers (113). The authors also concluded that these results may open a new avenue for research in the treatment of patients with LC and underlying COPD (113) as type II-EMT and angiogenesis (type-III EMT) favor lung tumor development (31).…”

Section: Chronic Inflammationmentioning

confidence: 74%

“…In this regard, tumor microenvironment induces immune suppression, reduces the efficacy of chemotherapy, and favors epithelial-to-mesenchymal transition (EMT) in the airways (type-II EMT, obliteration of small airways), which has recently emerged as a novel target for LC treatment (112). In line with this, a recent investigation showed that treatment of lung epithelial cells with CS extracts induced alveolar EMT through a cascade of biological mechanisms characterized by a rise in TGF-beta and Rac1/Smad2 signaling pathway (113). Interestingly, the blockade of TGF-beta activity attenuated EMT expression markers (113).…”

Section: Chronic Inflammationmentioning

confidence: 74%

Relationships between chronic obstructive pulmonary disease and lung cancer: biological insights

Barreiro¹,

Bustamante

Curull³

et al. 2016

J. Thorac. Dis.

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Lung cancer (LC) has become one of the leading causes of preventable death in the last few decades. Cigarette smoking (CS) stays as the main etiologic factor of LC despite that many other causes such as occupational exposures, air pollution, asbestos, or radiation have also been implicated. Patients with chronic obstructive pulmonary disease (COPD), which also represents a major cause of morbidity and mortality in developed countries, exhibit a significantly greater risk of LC. The study of the underlying biological mechanisms that may predispose patients with chronic respiratory diseases to a higher incidence of LC has also gained much attention in the last few years. The present review has been divided into three major sections in which different aspects have been addressed: (I) relevant etiologic agents of LC; (II) studies confirming the hypothesis that COPD patients are exposed to a greater risk of developing LC; and (III) evidence on the most relevant underlying biological mechanisms that support the links between COPD and LC. Several carcinogenic agents have been described in the last decades but CS remains to be the leading etiologic agent in most geographical regions in which the incidence of LC is very high. Growing evidence has put the line forward the implications of COPD and especially of emphysema in LC development. Hence, COPD represents a major risk factor of LC in patients. Different avenues of research have demonstrated the presence of relevant biological mechanisms that may predispose COPD patients to develop LC. Importantly, the so far identified biological mechanisms offer targets for the design of specific therapeutic strategies that will further the current treatment options for patients with LC. Prospective screening studies, in which patients with COPD should be followed up for several years will help identify biomarkers that may predict the risk of LC among these patients.

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“…These results suggest that RCC2 is involved in LCPAT1-regulated autophagy and EMT. Shen et al reported that Rac1 mediated the smoking-induced autophagy [51]. Another study found that RCC2 could bind to Rac1 [47] and acted as a dual regulator of Rac1 and Arf6 to further influence cell migration and movement [52].…”

Section: Discussionmentioning

confidence: 99%

LncRNA LCPAT1 Mediates Smoking/ Particulate Matter 2.5-Induced Cell Autophagy and Epithelial-Mesenchymal Transition in Lung Cancer Cells via RCC2

Lin

Zhang

Feng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ecological studies have shown that air pollution and prevalence of cigarette smoking are positively correlated. Evidence also suggests a synergistic effect of cigarette smoking and PM2.5 exposure (Environmental Particulate Matter ≤ 2.5 µm in diameter) on lung cancer risk. We aimed to evaluate the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality and determine its underlying mechanisms in vitro. Methods: “MOVER” method was used to analyze the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality. Cell autophagy and malignant behaviors induced by cigarette smoke extract (CSE) and PM2.5 exposure were examined in vitro. Gene expression was examined by qRT-PCR and western blot. RNA and protein interaction was determined using a RNA binding protein immunoprecipitation assay. Results: An increased risk for lung cancer death (RERI (the relative excess risk) =0.28) was observed with a synergistic interaction between cigarette smoking and PM2.5 pollution. Cell migration, invasion, EMT (epithelial-mesenchymal transition) and autophagy were elevated when lung cancer cells were treated with CSE and PM2.5 in combination. A lncRNA, named lung cancer progression-association transcript 1 (LCPAT1), was up-regulated after the treatment of CSE and PM2.5, and knocking down the lncRNA impaired the effect of CSE and PM2.5 on lung cancer cells. In addition, LCPAT1 was shown to bind to RCC2, and RCC2 mediated the effect of LCPAT1 on cell autophagy, migration, invasion and EMT in lung cancer. Conclusions: Our results suggest that combined exposure to CSE and PM2.5 induces LCPAT1 expression, which up-regulates autophagy, and promotes lung cancer progression via RCC2.

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Cigarette smoke-induced alveolar epithelial–mesenchymal transition is mediated by Rac1 activation

Cited by 60 publications

References 40 publications

Gelsolin Promotes Radioresistance in Non–Small Cell Lung Cancer Cells Through Activation of Phosphoinositide 3-Kinase/Akt Signaling

Gelsolin Promotes Radioresistance in Non–Small Cell Lung Cancer Cells Through Activation of Phosphoinositide 3-Kinase/Akt Signaling

Relationships between chronic obstructive pulmonary disease and lung cancer: biological insights

LncRNA LCPAT1 Mediates Smoking/ Particulate Matter 2.5-Induced Cell Autophagy and Epithelial-Mesenchymal Transition in Lung Cancer Cells via RCC2

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