Pulmonary Cell News Volume 6.00 | Jan 5 2017

TOP STORY

Role of CPS1 in Cell Growth, Metabolism, and Prognosis in LKB1-Inactivated Lung Adenocarcinoma

Liver kinase B1 (LKB1) is a tumor suppressor in lung adenocarcinoma (LADC). Researchers investigated the proteomic profiles of 45 LADC cell lines with and without LKB1 inactivation. [J Natl Cancer Inst] Abstract

(Ranked by impact factor of the journal)

Glucocorticoid Insensitivity in Virally Infected Airway Epithelial Cells Is Dependent on Transforming Growth Factor-β Activity

The authors examined the contribution of transforming growth factor-β activity to the glucocorticoids-resistance caused by viral infection. They demonstrated that viral infection of human bronchial epithelial cells with respiratory syncytial virus, rhinovirus or influenza A virus impairs GC anti-inflammatory action. [PLoS Pathog] Full Article

Targeted Epigenetic Editing of SPDEF Reduces Mucus Production in Lung Epithelial Cells

Scientists aimed to reduce lung epithelial mucus production by targeted silencing SAM-pointed domain-containing Ets-like factor (SPDEF) using the novel strategy epigenetic editing. Zinc fingers and CRISPR/dCas platforms were engineered to target repressors to the SPDEF promoter. All constructs were able to effectively suppress both SPDEF mRNA and protein expression, which was accompanied by inhibition of downstream mucus-related genes. [Am J Physiol Lung Cell Mol Physiol] Abstract

A Keratan Sulfate Disaccharide Prevents Inflammation and the Progression of Emphysema in Murine Models

Researchers showed that keratan sulfate (KS), one of the major glycosaminoglycans produced in the small airway, decreased in lungs of cigarette-smoke-exposed mice. In order to confirm the protective effect of KS in the small airway, a disaccharide repeating unit of KS designated L4 was administered to two murine models: elastase-induced-emphysema and LPS-induced exacerbation of a cigarette smoke-induced emphysema. They found that L4 consistently blocked the chemotactic migration of neutrophils in vitro. [Am J Physiol Lung Cell Mol Physiol] Abstract | Press Release

Molecular Genetic and Biochemical Responses in Human Airway Epithelial Cell Cultures Exposed to Titanium Nanoparticles In Vitro

Scientists aimed to investigate of cytotoxicity and changes in gene expression profiles influenced by commonly titanium nanoparticles in human alveolar epithelial and pharynx cell lines in vitro since inhalation is an important pathway for exposure to these nanoparticles. [J Biomed Mater Res A] Abstract

Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling

The authors sought to understand the role of basal cell (BC) and endothelial cells (EC) cross-talk in regulating BC stem/progenitor function. Using an in vitro co-culture system that mimics the in vivo physical separation of these cell types, they assessed the impact of primary lung microvascular EC on differentiation of primary BC into a mucociliated epithelium. [Stem Cell Rev] Abstract

LUNG CANCER

Pellino-1 Promotes Lung Carcinogenesis via the Stabilization of Slug and Snail through K63-Mediated Polyubiquitination

Scientist showed pellino-1-Tg mice developed adenocarcinoma in the lungs, and pellino-1 expression was higher in human lung adenocarcinoma cell lines compared with non-neoplastic bronchial epithelial cell lines. Pellino-1 overexpression increased the cell proliferation, survival, colony formation, invasion and migration of lung adenocarcinoma cells, whereas pellino-1 knock-down showed the opposite effect. [Cell Death Differ] Full Article

The Receptor Tyrosine Kinase AXL Mediates Nuclear Translocation of the Epidermal Growth Factor Receptor

The authors hypothesized that AXL mediated the nuclear translocation of EGFR in the setting of cetuximab resistance. Cetuximab-resistant clones of non–small cell lung cancer in culture and patient-derived xenografts in mice had increased abundance of AXL and nuclear EGFR (nEGFR). Cellular fractionation analysis, super-resolution microscopy, and electron microscopy revealed that genetic loss of AXL reduced the accumulation of nEGFR. [Sci Signal] Abstract

The Pseudogene DUXAP8 Promotes Non-Small Cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB

Researchers identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for non-small cell lung cancer patients. Knockdown of DUXAP8 impaired cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. [Mol Ther] Abstract

Protein Serine/Threonine Phosphatase PPEF-1 Suppresses Genotoxic Stress Response via Dephosphorylation of PDCD5

Investigators reported that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates programmed cell death 5 (PDCD5) at Ser-119, which leads to PDCD5 destabilization. They also determined that overexpression of wild-type PPEF-1, but not inactive PPEF-1^D172N, significantly increased tumorigenic growth and chemoresistance of A549 human lung carcinoma cells. [Sci Rep] Full Article

Non-Malignant Respiratory Epithelial Cells Preferentially Proliferate from Resected Non-Small Cell Lung Cancer Specimens Cultured under Conditionally Reprogrammed Conditions.

Using the conditionally reprogrammed cells method, four institutions independently cultured tumor tissues from 48 non-small cell lung cancers and 22 non-malignant lungs. The authors found that epithelial cells could be cultured from tumor and non-malignant lung, however epithelial cells cultured from tumors had features of non-malignant respiratory epithelial cells. [Oncotarget] Full Article

Podocalyxin Influences Malignant Potential by Controlling Epithelial Mesenchymal Transition in Lung Adenocarcinoma

Scientists aimed to clarify the role of podocalyxin (PODXL) over-expression in epithelial mesenchymal transition (EMT) in lung cancer, and determine the prognostic value of PODXL over-expression in tumors from lung cancer patients. Investigators examined the morphology, EMT marker expression, and migration and invasion abilities of engineered A549 PODXL-knockdown or PODXL-over-expression lung adenocarcinoma cells. [Cancer Sci] Full Article

The lncRNA XIST Exhibits Oncogenic Properties via Regulation of miR-449a and Bcl-2 in Human Non-Small Cell Lung Cancer

Researchers investigated the functional mechanisms of the long non-coding RNAs (lncRNA) XIST in two human non-small cell lung cancer (NSCLC) cell lines, A549 and NCI-H1299. In all the five NSCLC cell lines tested, the expression levels of XIST were significantly elevated, as compared with those in normal human bronchial epithelial cell line BEAS-2B. [Acta Pharmacol Sin] Full Article

Effects of Hypercapnia on the Lung

The authors provide a physiological and mechanistic perspective on the effects of hypercapnia on the lungs and discuss the recent understanding of CO₂ modulation of the alveolar epithelial function (lung edema clearance), epithelial cell repair, innate immunity and airway function. [J Physiol] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.

Dr. Fernando J. Martinez Named Chief of Division of Pulmonary and Critical Care Medicine at Weill Cornell Medicine and New York-Presbyterian Weill Cornell Medical Center

Dr. Fernando J. Martinez, a clinician and translational investigator who specializes in fibrotic lung disease and airway disorders including asthma and chronic obstructive pulmonary disease, has been named chief of the Division of Pulmonary and Critical Care Medicine at Weill Cornell Medicine and NewYork-Presbyterian Weill Cornell Medical Center. [Weill Cornell Medicine] Press Release

Bavarian Nordic Initiates Trial of CV301 in Combination with Nivolumab in Patients with Lung Cancer

Bavarian Nordic A/S announced the initiation of a clinical trial combining its proprietary cancer immunotherapy candidate, CV301, with the anti-PD-1 drug, OPDIVO^® (nivolumab) from Bristol-Myers Squibb. The study is enrolling patients with non-small cell lung cancer who have failed prior therapy. [Bavarian Nordic A/S] Press Release

US Scientists Fear New Restrictions on Fetal-Tissue Research

House Republicans conclude that tissue from aborted fetuses is of limited value for research and seek to reduce funding. [Nature News] Editorial

Argentina’s Researchers Occupy Science Ministry

Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. And the occupation seems to have paid off, in part: many of those involved have been offered extensions to their fellowships. [Nature News] Editorial

Scientists in Germany, Peru and Taiwan to Lose Access to Elsevier Journals

Thousands of scientists in Germany, Peru and Taiwan are preparing for a new year without online access to journals from the Dutch publishing giant Elsevier. Contract negotiations in both Germany and Taiwan broke down in December, while Peru’s government has cut off funding for a licence. [Nature News] Editorial

NEW 19^th International AEK Cancer Congress
March 1-3, 2017
Heidelberg, Germany

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Fellow – Lung Cancer (Massachusetts General Hospital)

NEW Allergy and Immunology – Postdoctoral Fellow (New York University Medical Center)

NEW Postdoctoral Research Fellow – Lung Injury and Repair (National Jewish Health)

PhD Positions – Heart and Lung Research (Max Planck Institute for Heart and Lung Research)

Postdoctoral Position – Cancer Epigenetics (Gustave Roussy Cancer Campus)

Postdoctoral Position – Targeted Approaches to Lung Cancers (University of California San Francisco)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Research Assistant/Associate(s) (University of Cambridge)

Postdoctoral Position – Heart, Lung and Blood Vascular Medicine (University of Pittsburgh)

Postdoctoral Fellow – System Genetics and Genomics of Lung Diseases (Brigham & Women’s Hospital – Harvard Medical School)

Postdoctoral Research Fellow – Cancer GeneticsEpigenetics (Fred Hutchinson Cancer Research Center)

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