Pulmonary Cell News Volume 7.12 | Mar 29 2018

TOP STORY

CK1α Suppresses Lung Tumor Growth by Stabilizing PTEN and Inducing Autophagy

The authors showed that in non-small-cell lung cancer, casein kinase 1 alpha 1 (CK1α) suppresses tumor growth by functioning as an autophagy inducer to activate an autophagy-regulating, tumor-suppressive PTEN/AKT/FOXO3a/Atg7 axis. [Nat Cell Biol] Abstract

(Ranked by impact factor of the journal)

Lung Epithelial Cells Coordinate Innate Lymphocytes and Immunity against Pulmonary Fungal Infection

Investigators demonstrated that NF-κB signaling in lung epithelial cells (LECs) is essential for immunity against the pulmonary fungal pathogen Blastomyces dermatitidis. LECs orchestrated innate antifungal immunity by augmenting the numbers of interleukin-17A- and granulocyte-macrophage colony-stimulating factor-producing innate lymphocytes, specifically “natural” Th17 cells. [Cell Host Microbe] Abstract | Graphical Abstract

Spatial-Temporal Lineage Restrictions of Embryonic p63⁺ Progenitors Establish Distinct Stem Cell Pools in Adult Airways

Using lineage-tracing and functional approaches in vivo, the authors showed that p63⁺ cells arising from the lung primordium are initially multipotent progenitors of airway and alveolar lineages, but later become restricted proximally to generate the tracheal adult stem cell pool. [Dev Cell] Full Article | Graphical Abstract

p53 in Bronchial Club Cells Facilitates Chronic Lung Inflammation by Promoting Senescence

To elucidate the function of airway epithelial p53 in inflammation, scientists subjected genetically modified mice, whose bronchial epithelial club cells lack p53, to repetitive inhalations of lipopolysaccharide, an exposure that leads to severe chronic bronchitis and airway senescence in wild-type mice. [Cell Rep] Full Article | Graphical Abstract

Heparin-Binding Epidermal Growth Factor Contributes to COPD Disease Severity by Modulating Airway Fibrosis and Pulmonary Epithelial-Mesenchymal Transition

In vitro, human bronchial epithelial cells and lung fibroblast cells exposed to the recombinant heparin-binding epidermal growth factor (HB-EGF), collagen deposition and epithelial-mesenchymal transition were assessed. Researchers found that sputum HB-EGF expression was significantly increased in patients with COPD compared with non-smokers and smokers without COPD. [Lab Invest] Abstract

LUNG CANCER

Developmental History Provides a Roadmap for the Emergence of Tumor Plasticity

In human non-small cell lung cancers, downregulation of the lung lineage-specifying TF NKX2-1 was associated with tumors bearing features of various gut tissues. Loss of Nkx2–1 from murine alveolar, but not airway, epithelium resulted in conversion of lung cells to gastric-like cells. [Dev Cell] Abstract | Press Release | Editorial | Graphical Abstract

Expansion of Airway Basal Epithelial Cells from Primary Human Non‐Small Cell Lung Cancer Tumors

Investigators report their experience regarding the derivation of primary non‐small cell lung cancer (NSCLC) cell cultures from 12 lung adenocarcinoma patients enrolled in the Tracking Cancer Evolution through Therapy clinical study and discuss these in the context of improving the success rate for in vitro cultivation of cells from NSCLC tumors. [Int J Cancer] Abstract

NF-κB-Driven Improvement of EHD1 Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancers

Researchers found that a lower Eps15 homology domain-containing (EHD) 1 expression improved both epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitors sensitivity, which was consistent with a lower CD133 expression, and progression-free survival in non-small cell lung cancer patients. The overexpression of EHD1 markedly increased erlotinib resistance and lung cancer cell stemness in vitro and in vivo. [Cell Death Dis] Full Article

Cigarette Smoke Enhances Oncogene Addiction to c‐MET and Desensitizes EGFR-Expressing Non‐Small Cell Lung Cancer to EGFR TKIs

Scientists showed that chronic exposure to cigarette smoke extract or tobacco smoke‐derived carcinogen benzo[α]pyrene, but not NNK, reduced the sensitivity of wild‐type epidermal growth factor receptor (EGFR)-expressing non‐small cell lung cancer cells to EGFR tyrosine kinase inhibitors (TKIs). [Mol Oncol] Abstract | Full Article

Matrix Remodeling in Chronic Lung Diseases

The authors consider how extracellular matrix molecules regulate lung homeostasis and their reorganization under pathological conditions that can modulate the inflammatory diseases asthma, COPD, and idiopathic pulmonary fibrosis. [Matrix Biol] Abstract

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

Verona Pharma Reports Positive Top-Line Data from Phase IIb Clinical Trial of RPL554 for Maintenance Treatment of COPD

Verona Pharma plc announced positive top-line data from its Phase IIb study evaluating RPL554, a first-in-class, inhaled, dual inhibitor of the enzymes phosphodiesterase 3 and 4 with bronchodilator and anti-inflammatory properties, as a maintenance treatment for COPD. [Verona Pharma plc] Press Release

ARMO BioSciences Enrolls First Patient in the CYPRESS 2 Trial Evaluating AM0010 in Non-Small Cell Lung Cancer

ARMO BioSciences, Inc. announced enrollment of its first patient in CYPRESS 2, a randomized Phase IIb trial designed to investigate pegilodecakin (AM0010) in combination with nivolumab as a second-line treatment for patients with metastatic non-small cell lung cancer. [ARMO BioSciences, Inc.] Press Release

Insmed Submits New Drug Application to FDA for ALIS in NTM Lung Disease Caused by MAC

Insmed Incorporated announced that it has submitted its New Drug Application for ALIS (Amikacin Liposome Inhalation Suspension) to the FDA for adult patients with nontuberculous mycobacterial (NTM) lung disease caused by Mycobacterium avium complex (MAC). [Insmed Incorporated] Press Release

Frances Shepherd Wins Canada Gairdner Wightman Award

University of Toronto Medicine Professor Frances Shepherd — an innovator in the study and treatment of lung cancer — has won the 2018 Canada Gairdner Wightman Award for outstanding career leadership in medicine and medical science. [University of Toronto] Press Release

NIH Moves to Punish Researchers Who Violate Confidentiality in Proposal Reviews

Late last year, National Institutes of Health (NIH) officials disclosed that they had discovered that someone involved in the proposal review process had violated confidentiality rules designed to protect its integrity. As a result, the agency announced in December 2017 that it would re-review dozens of applications that might have been compromised. Now, NIH says it has completed re-evaluating 60 applications and has also begun taking disciplinary action against researchers who broke its rules. [ScienceInsider] Editorial

India Taps Biologist as New Science Adviser

India has a new science adviser. Prime Minister Narendra Modi’s government tapped Krishnaswamy VijayRaghavan, a molecular biologist and head of India’s Department of Biotechnology, to fill the post. [ScienceInsider] Editorial

NEW 6^th Annual German Stem Cell Network (GSCN) Conference
September 19-21, 2018
Heidelberg, Germany

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

NEW Postdoctoral Position – Cell and Molecular Biology (Helmholtz Zentrum München)

Research Technologist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Position – Cancer, Immunotherapy, and Fibrosis (University of Alabama at Birmingham)

Senior Research Scientist – Lung Epithelium (AstraZeneca)

Research Scientist – Cell Biologist (MedImmune)

Full Professorship and Director – Lung Biology (Ludwig-Maximilians-Universität München)

Postdoctoral Traveling Fellowship – Lung Cancer (Cancer Research UK)

Doctoral Researcher Positions – Deciphering Therapeutic Targets in Lung Toxicology (Ludwig-Maximilians-Universität München)

Postdoctoral Position – Immune Oncology (H. Lee Moffitt Cancer & Research Institute)

Postdoctoral Scholar – Autoimmune Diseases Affecting the Lung (University of California, San Francisco)

Assistant Professor – Pulmonary Physiology (University of California, Riverside)

Multiple Positions – Pulmonary (University of Alabama at Birmingham)

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