scholarly journals Deficiency of Functional Iron-Sulfur Domains in ABCE1 Inhibits the Proliferation and Migration of Lung Adenocarcinomas By Regulating the Biogenesis of Beta-Actin In Vitro

2017 ◽  
Vol 44 (2) ◽  
pp. 554-566 ◽  
Author(s):  
Qian Yu ◽  
Xu Han ◽  
Da-Li Tian
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
A549 Cells ◽  
Metastatic Progression ◽  
Lung Cancer Metastasis ◽  
And Migration ◽  
Opposing Effects ◽  
Proliferation And Migration

Background/Aims: ATP-binding cassette transporter E1 (ABCE1), a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. Methods: The interaction between ABCE1 and β-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD) cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1). The role of Fe-S clusters in the viability and migration of cancer cells was evaluated using clonogenic, MTT, Transwell and wound healing assays. Cytoskeletal rearrangement was determined using immunofluorescent techniques. Results: Fe-S clusters were the key domains in ABCE1 involved in binding to β-actin. The proliferative and migratory capacity increased in cells overexpressing ABCE1. However, the absence of Fe-S clusters reversed these effects. A549 cells overexpressing ABCE1 exhibited irregular morphology and increased levels of cytoskeletal polymerization as indicated by the immunofluorescence images. In contrast, cells expressing the Fe-S cluster deletion mutant presented opposing effects. Conclusion: These results demonstrate the indispensable role of Fe-S clusters when ABCE1 participates in the proliferation and migration of LUADs by interacting with β-actin. The Fe-S clusters of ABCE1 may be potential targets for the prevention of lung cancer metastasis.

Anti-Metastatic Effects of Lupeol via the Inhibition of MAPK/ERK Pathway in Lung Cancer

2020 ◽  
Vol 21 (2) ◽  
pp. 201-206 ◽  
Author(s):  
Mital Bhatt ◽  
Mitesh Patel ◽  
Mohd Adnan ◽  
Mandadi N. Reddy
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
A549 Cells ◽  
Cancer Therapeutics ◽  
Enzyme Linked Immunosorbent Assay ◽  
Erk Pathway ◽  
Cytotoxic Effects ◽  
Lung Cancer Metastasis

Background and Objective: ERK pathway is one of the most crucial pathways in lung cancer metastasis. Targeting its pathway is decisive in lung cancer research. Thus, this study demonstrated for the first time a significant and selective anti-metastatic effects of lupeol against lung cancer A549 cells via perturbations in the ERK signaling pathway. Materials and Methods: Human protein targets of lupeol were predicted in silico. Migration and cytotoxicity assays were carried out in vitro. Expression levels of proteins Erk1/2 and pErk1/2 were ensured using Enzyme-Linked Immunosorbent Assay (ELISA). Semi-quantitative RT-PCR technique was used to estimate changes in crucial mesenchymal marker geneexpression levels of Ncadherin and vimentin. Results: Lupeol was found to target ERK and MEK proteins effectively. Despite having no cytotoxic effects, lupeol also significantly inhibited cell migration in A549 cells with decreased expression of the pErk1/2 protein along with N-cadherin and vimentin genes. Conclusion: Lupeol inhibits cell migration, showed no cytotoxic effects on A549 cells, decreased pErk1/2 and EMT gene expression. Thus, it can serve as a potential ERK pathway inhibitor in lung cancer therapeutics.

In-vitro Pre-Treatment of Cancer Cells with TGF-β1: A Novel Approach of Tail Vein Lung Cancer Metastasis Mouse Model for Anti-Metastatic Studies

2019 ◽  
Vol 12 (4) ◽  
pp. 249-260 ◽  
Author(s):  
Ghulam Jilany Khan ◽  
Li Sun ◽  
Muhammad Abbas ◽  
Muhammad Naveed ◽  
Talha Jamshaid ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Cancer Metastasis ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Lung Cancer Metastasis ◽  
Pre Treatment ◽  
Tgf Β1

Background: Aggressive behavior of tumor metastasis comes from certain mutations, changes in cellular metabolic and signaling pathways that are majorly altered by tumor microenvironment (TME), its other components and growth factors like transforming growth factor-β1 (TGF-β1) which is chiefly known for its epithelial to mesenchymal transformation (EMT). EMT is a critical step of metastasis cascade in actual human lung cancer scenario. Objective: Our present study is focused on unveiling the in-vivo metastatic behavior of TGF-β1 treated lung cancer cells that undergo EMT. Methods: The lung cancer epithelial A549 cells were treated in-vitro with TGF-β1 (3-5ng/ml for 72 h) for EMT. After confirming the transformation of cells by phenotype modifications, wound healing and cell migration assay and qRT-PCR analyses of EMT biomarkers including E. Cadherin, Vimentin, Snail, Slug, MMP2 and MMP9; those TGF-β1 modified cells were probed with fluorescent trackers and were injected into the tail vein of BALB/c nude mice for metastatic dissemination studies. Results: Our findings indicate that the distribution of TGF-β1 treated A549 cells as compared to W.T A549 towards lungs is less in terms of total relative fluorescent cluster count, however, the difference is insignificant (52±4, 60±5 respectively). Additionally, we show that TGF-β1 treated cells tend to metastasize almost 2, 3, 1.5, 2 and 1.7 times more than W.T towards liver, brain, ovaries, bones and adrenal gland, respectively, which is very much like human lung cancer metastasis. Conclusion: Conclusively, it is the first study ever reporting that a pre-treatment of cells with TGF-β1 for experimental lung cancer metastasis mouse model may portray a more precise approach for the development of potential therapeutic treatments. Additional pre-treatment studies with the application of other TME conditions like hypoxia and factors like NFκB, VEGF etc. may be a future prospect to develop a better understanding.

scholarly journals The role of exosomes in lung cancer metastasis and clinical applications: an updated review

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lei Yin ◽  
Xiaotian Liu ◽  
Xuejun Shao ◽  
Tao Feng ◽  
Jun Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Cancer Cell ◽  
Cancer Metastasis ◽  
Value Assessment ◽  
Lung Carcinogenesis ◽  
Research Attention ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis

AbstractLung cancer is the leading cause of cancer-associated deaths accounting for 24% of all cancer deaths. As a crucial phase of tumor progression, lung cancer metastasis is linked to over 70% of these mortalities. In recent years, exosomes have received increasing research attention in their role in the induction of carcinogenesis and metastasis in the lung. In this review, recent studies on the contribution of exosomes to lung cancer metastasis are discussed, particularly highlighting the role of lung tumor-derived exosomes in immune system evasion, epithelial-mesenchymal transition, and angiogenesis, and their involvement at both the pre-metastatic and metastatic phases. The clinical application of exosomes as therapeutic drug carriers, their role in antitumor drug resistance, and their utility as predictive biomarkers in diagnosis and prognosis are also presented. The metastatic activity, a complex multistep process of cancer cell invasion, survival in blood vessels, attachment and subsequent colonization of the host's organs, is integrated with exosomal effects. Exosomes act as functional mediating factors in cell–cell communication, influencing various steps of the metastatic cascade. To this end, lung cancer cell-derived exosomes enhance cell proliferation, angiogenesis, and metastasis, regulate drug resistance, and antitumor immune activities during lung carcinogenesis, and are currently being explored as an important component in liquid biopsy assessment for diagnosing lung cancer. These nano-sized extracellular vesicles are also being explored as delivery vehicles for therapeutic molecules owing to their unique properties of biocompatibility, circulatory stability, decreased toxicity, and tumor specificity. The current knowledge of the role of exosomes highlights an array of exosome-dependent pathways and cargoes that are ripe for exploiting therapeutic targets to treat lung cancer metastasis, and for predictive value assessment in diagnosis, prognosis, and anti-tumor drug resistance.

Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro

Life Sciences ◽  
2021 ◽  
Vol 276 ◽  
pp. 119436
Author(s):  
Keshav Raj Paudel ◽  
Ridhima Wadhwa ◽  
Xin Nee Tew ◽  
Natalie Jia Xin Lau ◽  
Thiagarajan Madheswaran ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Liquid Crystalline ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Proliferation ◽  
Liquid Crystalline Nanoparticles ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Salidroside Suppresses the Proliferation and Migration of Human Lung Cancer Cells through AMPK-Dependent NLRP3 Inflammasome Regulation

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Weidong Ma ◽  
Ziyuan Wang ◽  
Yan Zhao ◽  
Qibin Wang ◽  
Yonghong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Nlrp3 Inflammasome ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Human Lung Cancer Cells ◽  
And Migration ◽  
Proliferation And Migration

Inflammatory reactions mediated by the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome contributes to non-small-cell lung cancer (NSCLC) progression, particularly in patients with bacterial infections. Salidroside (SAL) has recently been shown to suppress lipopolysaccharide- (LPS-) induced NSCLC proliferation and migration, but its mechanism of action remains unclear. It has been shown that SAL improves metabolic inflammation in diabetic rodents through AMP-activated protein kinase- (AMPK-) dependent inhibition of the NLRP3 inflammasome. However, whether the NLRP3 inflammasome is regulated by SAL in NSCLC cells and how its underlying mechanism(s) can be determined require clarification. In this study, human lung alveolar basal carcinoma epithelial (A549) cells were treated with LPS, and the effects of SAL on cell proliferation, migration, AMPK activity, reactive oxygen species (ROS) production, and NLRP3 inflammasome activation were investigated. We found that LPS induction increases the proliferation and migration of A549 cells which was suppressed by SAL. Moreover, SAL protected A549 cells against LPS-induced AMPK inhibition, ROS production, and NLRP3 inflammasome activation. Blocking AMPK using Compound C almost completely suppressed the beneficial effects of SAL. In summary, these results indicate that SAL suppresses the proliferation and migration of human lung cancer cells through AMPK-dependent NLRP3 inflammasome regulation.

scholarly journals Knockdown of LncRNA LINC00958 Inhibits the Proliferation and Migration of NSCLC Cells by MiR-204-3p/KIF2A Axis

2021 ◽  
Vol 30 ◽  
pp. 096368972110255
Author(s):  
Qing Wang ◽  
Kai Li ◽  
Xiaoliang Li
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence suggests that long non-coding RNAs (lncRNAs) function in the tumorigenesis of NSCLC. LINC00958, a newly identified lncRNA, has been reported to be closely linked to tumorigenesis in several cancers. However, its specific role in NSCLC remains unclear. In this study, we determined the expression of LINC00958 in NSCLC by RT-qPCR analysis and evaluated cell proliferation and migration by CCK-8 and transwell assays, respectively. We established a xenograft tumor model to examine the effect of LINC00958 on tumor growth in vivo. Luciferase reporter assays were performed to determine the interaction between LINC00958 and miR-204-3p and the interaction between miR-204-3p and KIF2A. We found that LINC00958 was up-regulated in NSCLC tissues and cell lines. Down-regulation of LINC00958 inhibited cell proliferation and migration in vitro and suppressed tumor growth in vivo. Besides, miR-204-3p was identified as a target of LINC00958 and miR-204-3p inhibitor could reverse the inhibitory effect of LINC00958 knockdown on proliferation and migration of NSCLC cells. We also validated that KIF2A, a direct target of miR-204-3p, was responsible for the biological role of LINC00958. KIF2A antagonized the effect of miR-204-3p on NSCLC cell proliferation and migration and was regulated by LINC00958/miR-204-3p. Taken together, these data indicate that the LINC00958/miR-204-3p/KIF2A axis is critical for NSCLC progression, which might provide a potential therapeutic target of NSCLC.

scholarly journals Attenuating role of withaferin A in the proliferation and migration of lung cancer cells via a p53‑miR‑27a/miR‑10b pathway

2021 ◽  
Vol 21 (3) ◽  
Author(s):  
Chen-Chu Lin ◽  
Tsung-Ying Yang ◽  
Hseuh-Ju Lu ◽  
Chen-Kai Wan ◽  
Shih-Lan Hsu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Lung Cancer Cells ◽  
Withaferin A ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals CEACAM5 stimulates the progression of non-small-cell lung cancer by promoting cell proliferation and migration

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095947
Author(s):  
Xinwen Zhang ◽  
Xingbao Han ◽  
Pengli Zuo ◽  
Xiuying Zhang ◽  
Hongbang Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell ◽  
Clinicopathological Features ◽  
Small Cell Lung ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Human Nsclc ◽  
Proliferation And Migration

Objective To detect the expression of CEA-related cell adhesion molecule 5 (CEACAM5) in non-small-cell lung cancer (NSCLC) and explore its function in the progression and development of NSCLC. Methods qRT-PCR and immunohistochemistry were performed to detect CEACAM5 expression in human NSCLC tissues and cell lines. The correlation between CEACAM5 expression and the clinicopathological features of patients with NSCLC was also investigated. MTT, colony formation, wound healing, and immunoblot assays were performed to detect the functions of CEACAM5 in NSCLC cells in vitro, and immunoblotting was used to detect the effects of CEACAM5 on p38–Smad2/3 signaling. Results CEACAM5 expression was elevated in human NSCLC tissues and cells. We further found that CEACAM expression was correlated with clinicopathological features including T division, lymph invasion, and histological grade in patients with NSCLC. The in vitro assays confirmed that CEACAM5 depletion inhibited the proliferation and migration of NSCLC cells by activating p38–Smad2/3 signaling. We verified the involvement of CEACAM5 in the suppression of NSCLC tumor growth in mice. Conclusion CEACAM5 stimulated the progression of NSCLC by promoting cell proliferation and migration in vitro and in vivo. CEACAM5 may serve as a potential therapeutic target for the treatment of NSCLC.

scholarly journals MicroRNA in Lung Cancer Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 265 ◽  
Author(s):  
Shang-Gin Wu ◽  
Tzu-Hua Chang ◽  
Yi-Nan Liu ◽  
Jin-Yuan Shih
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Cancer Treatments ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Targeted Treatments

Tumor metastasis is a hallmark of cancer, with distant metastasis frequently developing in lung cancer, even at initial diagnosis, resulting in poor prognosis and high mortality. However, available biomarkers cannot reliably predict cancer spreading sites. The metastatic cascade involves highly complicated processes including invasion, migration, angiogenesis, and epithelial-to-mesenchymal transition that are tightly controlled by various genetic expression modalities along with interaction between cancer cells and the extracellular matrix. In particular, microRNAs (miRNAs), a group of small non-coding RNAs, can influence the transcriptional and post-transcriptional processes, with dysregulation of miRNA expression contributing to the regulation of cancer metastasis. Nevertheless, although miRNA-targeted therapy is widely studied in vitro and in vivo, this strategy currently affords limited feasibility and a few miRNA-targeted therapies for lung cancer have entered into clinical trials to date. Advances in understanding the molecular mechanism of metastasis will thus provide additional potential targets for lung cancer treatment. This review discusses the current research related to the role of miRNAs in lung cancer invasion and metastasis, with a particular focus on the different metastatic lesions and potential miRNA-targeted treatments for lung cancer with the expectation that further exploration of miRNA-targeted therapy may establish a new spectrum of lung cancer treatments.

Abstract 2290: More than a biomarker: Studying the role of vimentin in lung cancer metastasis

2015 ◽  
Author(s):  
Alessandra M. Salgueiro ◽  
Melissa Gilbert-Ross ◽  
Lauren S. Havel ◽  
John Shupe ◽  
Adam I. Marcus
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
Lung Cancer Metastasis
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