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https://www.readbyqxmd.com/read/28646553/epithelial-mesenchymal-transition-emt-a-spectrum-of-states-role-in-lung-development-homeostasis-and-disease
#1
REVIEW
Mohit Kumar Jolly, Chris Ward, Mathew Suji Eapen, Stephen Myers, Oskar Hallgren, Herbert Levine, Sukhwinder Singh Sohal
Epithelial Mesenchymal Transition (EMT) plays key roles during lung development and many lung diseases such as Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis. Here, integrating morphological observations with underlying molecular mechanisms, we highlight the functional role of EMT in lung development and injury repair, and discuss how it can contribute to pathogenesis of chronic lung disease. We discuss the evidence of manifestation of EMT and its potential driving role in COPD, idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS), and lung cancer, while noting that all cells need not display a full EMT in any of these contexts, i...
June 24, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28642450/cbp501-inhibits-egf-dependent-cell-migration-invasion-and-epithelial-to-mesenchymal-transition-of-non-small-cell-lung-cancer-cells-by-blocking-kras-to-calmodulin-binding
#2
Naoya Saito, Naoki Mine, Donald W Kufe, Daniel D Von Hoff, Takumi Kawabe
The anti-cancer agent CBP501 binds to calmodulin (CaM). Recent studies showed that migration and metastasis are inhibited by several CaM antagonists. However, there is no available evidence that CBP501 has similar effects. Here we found that CBP501 inhibits migration of non-small cell lung cancer (NSCLC) cells in vitro, even in the presence of migration inducing factors such as WNT, IL-6, and several growth factors. CBP501 also inhibited epidermal growth factor (EGF) enhanced invasion and the epithelial-to-mesenchymal transition (EMT), and this inhibition was accompanied by (i) suppression of Akt and ERK1/2 phosphorylation, and (ii) suppression of expression of transcription factor Zeb1 and the mesenchymal marker Vimentin...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642260/cigarette-smoke-disrupts-monolayer-integrity-by-altering-epithelial-cell-cell-adhesion-and-cortical-tension
#3
Kristine Nishida, Kieran A Brune, Nirupama Putcha, Pooja Mandke, Wanda K O'Neal, Danny Shade, Vasudha Srivastava, Menghen Wang, Hong Lam, Steven S An, M Bradley Drummond, Nadia N Hansel, Douglas N Robinson, Venkataramana K Sidhaye
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Cigarette smoke (CS) drives disease development and progression. The epithelial barrier is damaged by CS with increased monolayer permeability. However, the molecular changes that cause this barrier disruption and the interaction between adhesion proteins and the cytoskeleton are not well defined. We hypothesized that CS alters monolayer integrity by increasing cell contractility and decreasing cell adhesion in epithelia...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28642042/changes-in-biophysical-membrane-properties-induced-by-the-budesonide-hydroxy-%C3%AE-cyclodextrin-complex
#4
Andreia G Dos Santos, Jules Bayiha, Gilles Dufour, Didier Cataldo, Brigitte Evrard, Liana C Silva, Magali Deleu, Marie-Paule Mingeot-Leclercq
Budesonide (BUD), a poorly soluble anti-inflammatory drug, is used to treat patients suffering from asthma and COPD (Chronic Obstructive Pulmonary Disease). Hydroxypropyl-β-cyclodextrin (HPβCD), a biocompatible cyclodextrin known to interact with cholesterol, is used as a drug-solubilizing agent in pharmaceutical formulations. Budesonide administered as an inclusion complex within HPβCD (BUD:HPβCD) required a quarter of the nominal dose of the suspension formulation and significantly reduced neutrophil induced inflammation in a COPD mouse model exceeding the effect of each molecule administered individually...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28638955/lipopolysaccharide-induced-ccn1-production-enhances-interleukin-6-secretion-in-bronchial-epithelial-cells
#5
Lin Shi, Nian Dong, Dongxiang Ji, Xiaomin Huang, Zhaojian Ying, Xiangdong Wang, Chengshui Chen
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical complication caused by primary or secondary lung injury, as well as by systemic inflammation. Researches regarding molecular pathophysiology of ALI/ARDS are immerging with an ultimate aim towards developing prognostic molecular biomarkers and molecule-based therapy. However, the molecular mechanisms concerning ALI/ARDS are still not completely understood. The purpose of the present study was to identify a crucial role of CCN1 in inflammatory microenvironment during ALI/ARDS and focus on a potential communication between CCN1 and interleukin-6 (IL-6) in the airway epithelial cells...
June 21, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28638804/pkc-%C3%AE-marcks-signaling-promotes-intracellular-survival-of-unopsonized-burkholderia-thailandensis
#6
Sofiya N Micheva-Viteva, Yulin Shou, Kumkum Ganguly, Terry H Wu, Elizabeth Hong-Geller
Pathogenic Burkholderia rely on host factors for efficient intracellular replication and are highly refractory to antibiotic treatment. To identify host genes that are required by Burkholderia spp. during infection, we performed a RNA interference (RNAi) screen of the human kinome and identified 35 host kinases that facilitated Burkholderia thailandensis intracellular survival in human monocytic THP-1 cells. We validated a selection of host kinases using imaging flow cytometry to assess efficiency of B. thailandensis survival in the host upon siRNA-mediated knockdown...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28638464/overexpression-of-pak1-correlates-with-aberrant-expression-of-emt-markers-and-poor-prognosis-in-non-small-cell-lung-cancer
#7
Zhiying Yang, Heran Wang, Longzheng Xia, Linda Oyang, Yujuan Zhou, Baihua Zhang, Xiaoyan Chen, Xia Luo, Qianjin Liao, Jianping Liang
Objective: p21-activated kinases (PAKs) are serine/threonine protein kinases. PAK1 and epithelial-mesenchymal transition (EMT) are key therapeutic targets in cancer. The clinical significance of PAK1 and its potential association with EMT phenotype in non-small cell lung cancer (NSCLC) was investigated. Methods: Immunohistochemistry was used to detect the expression of PAK1, and mesenchymal and epithelial markers (vimentin, N-cadherin, and E-cadherin) in 186 cases of NSCLC tissues and 50 cases of tumor-adjacent normal tissues...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28637674/oxidative-stress-destabilizes-protein-arginine-methyltransferase-4-via-glycogen-synthase-kinase-3%C3%AE-to-impede-lung-epithelial-cell-migration
#8
Xiuying Li, Yandong Lai, Jin Li, Mingyi Zou, Chunbin Zou
Oxidative stress impacts normal cellular function leading to the pathogenesis of various diseases including pulmonary illnesses. Protein arginine methyltransferase 4 (PRMT4) is critical for normal lung alveolar epithelial cell development; however, the regulation of PRMT4 within such pulmonary diseases has yet to be elucidated. Using biochemical approaches, we uncovered that peroxide (H2O2) treatment decreases PRMT4 protein stability in murine lung epithelial (MLE12) cells to impede cell migration. Protein kinase glycogen synthase kinase 3β (GSK-3β) interacts with PRMT4 and catalyzes PRMT4 T132 phosphorylation that protects PRMT4 from ubiquitin proteasomal degradation...
June 21, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28637482/microrna-200c-and-microrna-141-are-regulated-by-a-foxp3-kat2b-axis-and-associated-with-tumor-metastasis-in-breast-cancer
#9
Guangxin Zhang, Wei Zhang, Bingjin Li, Erica Stringer-Reasor, Chengjing Chu, Liyan Sun, Sejong Bae, Dongquan Chen, Shi Wei, Kenneth Jiao, Wei-Hsiung Yang, Ranji Cui, Runhua Liu, Lizhong Wang
BACKGROUND: Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. METHODS: We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 (sf/+) ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family...
June 21, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28637465/early-pulmonary-response-is-critical-for-extra-pulmonary-carbon-nanoparticle-mediated-effects-comparison-of-inhalation-versus-intra-arterial-infusion-exposures-in-mice
#10
Koustav Ganguly, Dariusch Ettehadieh, Swapna Upadhyay, Shinji Takenaka, Thure Adler, Erwin Karg, Fritz Krombach, Wolfgang G Kreyling, Holger Schulz, Otmar Schmid, Tobias Stoeger
BACKGROUND: The death toll associated with inhaled ambient particulate matter (PM) is attributed mainly to cardio-vascular rather than pulmonary effects. However, it is unclear whether the key event for cardiovascular impairment is particle translocation from lung to circulation (direct effect) or indirect effects due to pulmonary particle-cell interactions. In this work, we addressed this issue by exposing healthy mice via inhalation and intra-arterial infusion (IAI) to carbon nanoparticles (CNP) as surrogate for soot, a major constituent of (ultrafine) urban PM...
June 20, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/28637014/a-combination-of-valproic-acid-sodium-salt-chir99021-e-616452-tranylcypromine-and-3-deazaneplanocin-a-causes-stem-cell-like-characteristics-in-cancer-cells
#11
Shuang Sha, Yuanfen Zhai, Chengzhao Lin, Heyong Wang, Qing Chang, Shuang Song, Mingqiang Ren, Gentao Liu
Many studies are based on the hypothesis that recurrence and drug resistance in lung carcinoma are due to a subpopulation of cancer stem-like cells (CSLCs) in solid tumors. Therefore it is crucial to screen for and recognize lung CSLCs. In this study, we stimulated non-small cell lung cancer (NSCLC) A549 cells to display stem cell-like characteristics using a combination of five small molecule compounds. The putative A549 stem cells activated an important CSLC marker, CD133 protein, as well multiple CSLC-related genes including ATP-binding cassette transporter G2 (ABCG2), C-X-C chemokine receptor type 4 (CXCR4), NESTIN, and BMI1...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636383/gene-expression-profiling-in-human-lung-cells-exposed-to-isoprene-derived-secondary-organic-aerosol
#12
Ying-Hsuan Lin, Maiko Arashiro, Phillip W Clapp, Tianqu Cui, Kenneth G Sexton, William Vizuete, Avram Gold, Ilona Jaspers, Rebecca C Fry, Jason Douglas Surratt
Secondary organic aerosol (SOA) derived from the photochemical oxidation of isoprene contributes a substantial mass fraction to atmospheric fine particulate matter (PM2.5). The formation of isoprene SOA is influenced largely by anthropogenic emissions through multiphase chemistry of its multi-generational oxidation products. Considering the abundance of isoprene SOA in the troposphere, understanding mechanisms of adverse health effects through inhalation exposure is critical to mitigating its potential impact on public health...
June 21, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28635228/-mechanism-of-long-non-coding-rna-metastasis-associated-lung-adenocarcinoma-transcript-1-induced-invasion-and-metastasis-of-esophageal-cancer-cell-ec-109
#13
Q Q Zhang, Y H Cui, Y Wang, W Z Kou, F Cao, X J Cao, Z H Miao, X H Kang
Objective: To investigate the effect and mechanism of long non-coding RNA-metastasis associated lung adenocarcinoma transcript 1, (LncRNA-MALAT1) on invasion and metastasis of esophageal cancer cell EC-109. Methods: EC-109 cells were transfected with lentiviral vector carrying short hairpin RNA of MALAT1( shRNA-MALAT1) or a nonspecific shRNA control (shRNA-control). The expressions of MALAT1, microRNA-200a, ZEB1 and ZEB2 were detected by qRT-PCR. The effect of shRNA-MALAT1 on invasion of EC-109 cells was determined by transwell assay...
June 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28635133/critical-role-of-glioma-associated-oncogene-homolog-1-in-maintaining-invasive-and-mesenchymal-like-properties-of-melanoma-cells
#14
I Ketut Gunarta, Rong Li, Ryota Nakazato, Ryusuke Suzuki, Jambaldorj Boldbaatar, Takeshi Suzuki, Katsuji Yoshioka
Cutaneous melanoma is the most aggressive form of skin cancer. This aggressiveness appears to be due to the cancer cells' ability to reversibly switch between phenotypes with non-invasive and invasive potentials, and microphthalmia-associated transcription factor (MITF) is known to play a central role in this process. The transcription factor glioma-associated oncogene homolog 1 (GLI1) is a component of the canonical and noncanonical sonic hedgehog pathways. Although GLI1 has been suggested to be involved in melanoma progression, its precise role and the mechanism underlying invasion remain unclear...
June 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28634241/psl-produced-by-mucoid-pseudomonas-aeruginosa-contributes-to-the-establishment-of-biofilms-and-immune-evasion
#15
Christopher J Jones, Daniel J Wozniak
Despite years of research and clinical advances, chronic pulmonary infections with mucoid Pseudomonas aeruginosa remain the primary concern for cystic fibrosis patients. Much of the research on these strains has focused on the contributions of the polysaccharide alginate; however, it is becoming evident that the neutral polysaccharide Psl also contributes to biofilm formation and the maintenance of chronic infections. Here, we demonstrate that Psl produced by mucoid strains has significant roles in biofilm structure and evasion of immune effectors...
June 20, 2017: MBio
https://www.readbyqxmd.com/read/28633480/a-prospective-examination-of-circulating-tumor-cell-profiles-in-non-small-cell-lung-cancer-molecular-subgroups
#16
C R Lindsay, V Faugeroux, S Michiels, E Pailler, F Facchinetti, D Ou, M V Bluthgen, C Pannet, M Ngo-Camus, G Bescher, C Caramella, F Billiot, J Remon, D Planchard, J-C Soria, B Besse, F Farace
Background: We report the first study examining the clinical, numerical and biological properties of circulating tumor cells (CTCs) according to molecular subtypes of non-small cell lung cancer (NSCLC). Patients and Methods: 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype and survival were assessed...
June 19, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28631574/microrna-125a-5p-plays-a-role-as-a-tumor-suppressor-in-lung-carcinoma-cells-by-directly-targeting-stat3
#17
Lou Zhong, Siyuan Sun, Jiahai Shi, Fei Cao, Xiao Han, Zhong Chen
Increasing evidence supports that the dysregulation of microRNA expression plays an important role in the process of tumor occurrence and development. Studies have found that mir-125a-5p expression was downregulated in a variety of tumors, but the effects and mechanism of mir-125a-5p in lung cancer are still unclear. The aim of this study is to detect the expression of mir-125a-5p in lung cancer tissues and lung cancer cell lines and to explore the effects of mir-125a-5p on the biological characteristics of lung cancer cells; thus, this study aims to provide new methods and new strategies for the treatment of lung cancer...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631571/a-truncated-p53-in-human-lung-cancer-cells-as-a-critical-determinant-of-proliferation-and-invasiveness
#18
Weiying Li, Baitang Lai, Xuehui Yang, Chunyan Zhang, Hui Wang
As a transcription factor, p53 must accumulate in the nucleus to be effective. Signals related to nuclear localization are distributed mainly in the C-terminal of p53. So these nuclear location domains were reserved and the other part of the C-terminal was removed in this study. We investigated whether the truncated p53 (p53(DEL)) may affect proliferation and invasive potential of human lung cancer cells. H1299 and 801D cells expressing full-length p53 and the p53(DEL) were obtained by screening. Cell proliferation assay, cell apoptotic analysis, cell migration assay, and invasion assay were performed...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631556/kruppel-like-factor-4-inhibits-non-small-cell-lung-cancer-cell-growth-and-aggressiveness-by-stimulating-transforming-growth-factor-%C3%AE-1-meidated-erk-jnk-nf-%C3%AE%C2%BAb-signaling-pathways
#19
Renzhi Yu, Lei Han, Xin Ni, Minghuan Wang, Ping Xue, Li Zhang, Mei Yuan
Non-small cell lung cancer is one of the most common epithelial tumors that cause the most common cancer-related mortality due to invasive ability. Research has found that Kruppel-like factor 4, a zinc-finger transcription factor, plays a critical role in the tumor evolution and progression. However, the molecular signal pathways mediated by Kruppel-like factor 4 in the progression of non-small cell lung cancer cells have not been well understood yet. In this study, we investigated the possible role and potential mechanism of Kruppel-like factor 4 in growth and aggressiveness of non-small cell lung cancer cells...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28630072/pseudomonas-quinolone-signal-pqs-induces-oxidative-stress-and-inhibits-heme-oxygenase-1-expression-in-lung-epithelial-cells
#20
Maher Y Abdalla, Traci Hoke, Javier Seravalli, Barbara L Switzer, Melissa Bavitz, Jill D Fliege, Peter J Murphy, Bradley E Britigan
Pseudomonas aeruginosa (PA) causes lung infection in patients with cystic fibrosis (CF). Pseudomonas Quinolone Signal (PQS) is a secreted PA virulence factor that contributes to the pathogenicity of PA. We were able to detect PQS in sputum samples from CF patients infected with PA, but not in samples from uninfected patients. We then tested the hypothesis that PQS induces oxidative stress in host cells by determining the ability of PQS to induce production of reactive oxygen species (ROS) in lung epithelial cells (A549 and primary normal human bronchial epithelial (NHBE)) and macrophages (J774A...
June 19, 2017: Infection and Immunity
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