Pulmonary Cell News Volume 6.12 | Mar 30 2017

TOP STORY

Transcription Factor Etv5 Is Essential for the Maintenance of Alveolar Type II Cells

The authors showed that the E26 transformation-specific family transcription factor Etv5 is essential to maintain alveolar type II (AT2) cell identity. Deletion of Etv5 from AT2 cells produced gene and protein signatures characteristic of differentiated alveolar type I cells. [Proc Natl Acad Sci USA] Full Article

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Cigarette Smoke Impairs A_2A Adenosine Receptor Mediated Wound Repair through Up-Regulation of Duox-1 Expression

Scientists hypothesized that cigarette smoke (CS) exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H₂O₂. They found that both CS extract (CSE) and CS treatment induced increased expression of Duox-1, and silencing of Doux-1 improved the rate of cell wound repair induced by CSE treatment. [Sci Rep] Full Article

The Role of miR-497/EIF3A Axis in TGFβ1-Induced Epithelial-Mesenchymal Transition and Extracellular Matrix in Rat Alveolar Epithelial Cells and Pulmonary Fibroblasts

Researchers chose a well-known TGFβ1-induced epithelial-mesenchymal transition (EMT) model in alveolar epithelial cells to investigate the functional role of EIF3A. TGFβ1 induced EIF3A expression and EMT process in alveolar epithelial cells, after EIF3A knockdown, the EMT process could be partially reversed. [J Cell Biochem] Abstract

LUNG CANCER

MOB1-YAP1/TAZ-NKX2.1 Axis Controls Bronchioalveolar Cell Differentiation, Adhesion and Tumor Formation

To investigate Mps One Binder Kinase Activator (MOB)1A/B’s roles in normal physiology and lung cancer, scientists generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice. Most mutants (70%) receiving Dox in utero died of hypoxia within one hour post-birth. Their alveolar epithelial cells showed increased proliferation, impaired YAP1/TAZ-dependent differentiation and decreased surfactant protein production, all features characteristic of human respiratory distress syndrome. [Oncogene] Abstract

IL-17C Mediates the Recruitment of Tumor-Associated Neutrophils and Lung Tumor Growth

Researchers investigated the function of interleukin-17C (IL-17C) in the pulmonary tumor microenvironment. They subjected mice deficient for IL-17C (IL-17C^−/−) and mice double deficient for Toll-like receptor 2 and 4 (TLR-2/4^−/−) to a metastatic lung cancer model. Tumor proliferation and growth as well as the number of tumor-associated neutrophils was significantly decreased in IL-17C^−/− and TLR-2/4^−/− mice exposed to nontypeable Haemophilus influenzae. [Oncogene] Abstract

Targeting CD47 and Autophagy Elicited Enhanced Antitumor Effects in Non-Small Cell Lung Cancer

The authors investigated the synergistic antitumor effect of simultaneously targeting CD47 and autophagy in non-small cell lung cancer (NSCLC). SIRPαD1-Fc, a novel CD47-targeting fusion protein, was generated and was found to increase the phagocytic and cytotoxic activities of macrophages against NSCLC cells. [Cancer Immunol Res] Abstract | Full Article

Tumor-Treating Fields Elicit a Conditional Vulnerability to Ionizing Radiation via the Downregulation of BRCA1 Signaling and Reduced DNA Double-Strand Break Repair Capacity in Non-Small Cell Lung Cancer Cell Lines

Tumor-treating fields (TTFields) are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. Using five non-small cell lung cancer (NSCLC) cell lines, scientists found that there is a variable response in cell proliferation and cell killing between these NSCLC cell lines that was independent of p53 status. TTFields treatment increased the G2/M population, with a concomitant reduction in S-phase cells followed by the appearance of a sub-G1 population indicative of apoptosis. [Cell Death Dis] Full Article

A Novel and Promising Therapeutic Approach for NSCLC: Recombinant Human Arginase Alone or Combined with Autophagy Inhibitor

Investigators report that recombinant human arginase (rhArg) could induce significant cytotoxicity and caspase-dependent apoptosis in non-small-cell lung cancer (NSCLC) cells. Their research revealed that rhArg dramatically stimulated autophagic response in NSCLC cells, which was proved by the formation and accumulation of autophagosomes and the conversion of microtubule-associated protein light chain 3 (LC3) from LC3-I to LC3-II. [Cell Death Dis] Full Article

TTF-1- and/or CD56-Positive Circulating Tumor Cells in Patients with Small Cell Lung Cancer (SCLC)

Scientists evaluated the phenotypic circulating tumor cells (CTCs) heterogeneity (TTF-1+ and/or CD56+) in SCLC patients and correlated it with the CellSearch. One-chemotherapy cycle decreased both the number of positive patients and their CTC number, irrespectively of their phenotype and the detection method. [Sci Rep] Full Article

Knockdown of Homeobox B5 (HOXB5) Inhibits Cell Proliferation, Migration, and Invasion in Non-Small Cell Lung Cancer Cells through Inactivation of the Wnt/β-Catenin Pathway

The authors showed that HOXB5 expression was elevated in human non-small cell lung cancer (NSCLC) tissues and cell lines. The in vitro experiments demonstrated that knockdown of HOXB5 inhibited the proliferation, migration and invasion, as well as prevented the EMT phenotype in NSCLC cells. [Oncol Res] Full Article

When Is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine

The authors summarize a body of work spanning nearly five decades amassed by a series of “lung epithelial cell biology pioneers” which carefully describes well characterized molecular, functional, and morphological features critical for discriminate assessment of an alveolar type II epithelial cell (AT2) phenotype. Armed with this they propose a series of core criteria to assist the field in confirming that cells obtained following a differentiating protocol are indeed mature and functional AT2 epithelial cells. [Am J Respir Cell Mol Biol] Abstract

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

Penn Studies Find Promise for Innovations in Liquid Biopsies

A series of studies from the Perelman School of Medicine at the University of Pennsylvania demonstrate the promise of new diagnostic methods for lung cancer. Three of the studies focus on liquid biopsies, an innovation which uses blood tests instead of surgical procedures in hopes of detecting cancer. [Press release from Perelman School of Medicine at the University of Pennsylvania discussing research presented at the 2017 American Association for Cancer Research Annual Meeting, Washington, D.C.] Press Release

Spectrum Pharmaceuticals Announces Initiation of a Phase II Trial of Poziotinib in Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations

Spectrum Pharmaceutical announced that the University of Texas MD Anderson Cancer Center initiated a Phase II trial of poziotinib in non-small cell lung cancer patients with EGFR exon 20 insertion mutations. [Spectrum Pharmaceuticals] Press Release

Horn to Lead Lung Cancer Combination Therapy Trial

Leora Horn, M.D., M.Sc., associate professor of Medicine and clinical director of the Thoracic Oncology Program at Vanderbilt-Ingram Cancer Center, has been selected to lead a clinical research trial of combination therapy using two targeted drugs for the treatment of a specific form of lung cancer. [Vanderbilt University Medical Center] Press Release

Aprea Therapeutics Announces Research Collaboration with Memorial Sloan Kettering Cancer Center

Aprea Therapeutics announced a collaboration with Memorial Sloan Kettering Cancer Center to study the effects of reactivation of tumor suppressor protein p53 by APR-246. The goal of the collaboration is to evaluate and characterize preclinical efficacy of APR-246 in combination with multiple other anti-cancer agents and across multiple tumor types. [Aprea Therapeutics] Press Release

Trump Wants 2018 NIH Cut to Come from Overhead Payments

The Trump administration could slash $5.8 billion from the 2018 budget of the National Institutes of Health (NIH), yet still fund as least as much research by eliminating overhead payments to universities and research institutions, Secretary of Health and Human Services Tom Price told lawmakers. [ScienceInsider] Editorial

European Commission Considering Leap into Open-Access Publishing

One of Europe’s biggest science spenders could soon branch out into publishing. The European Commission, which spends more than €10 billion annually on research, may follow two other big league funders, the Wellcome Trust and the Bill & Melinda Gates Foundation, and set up a “publishing platform” for the scientists it funds, in an attempt to accelerate the transition to open-access publishing in Europe. [ScienceInsider] Editorial

Europe Says University of California Deserves Broad Patent for CRISPR

The European Patent Office announced its “intention to grant a patent” to the University of California (UC) for its broad-based claims about the genome-editing tool popularly known as CRISPR. UC, on behalf of several parties, has been in a pitched battle with the Broad Institute of Cambridge, Massachusetts, over CRISPR patents, and the new decision marks a sharp departure from the position of the U.S. Patent and Trademark Office. [ScienceInsider] Editorial

NEW Keystone Symposium: Angiogenesis & Vascular Disease
May 8-12, 2017
Santa Fe, New Mexico, United States

NEW Keystone Symposium: Mitochondria, Metabolism & Heart
May 8-12, 2017
Santa Fe, New Mexico,, United States

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

NEW NIH Training Grant – Pediatric Pulmonary Medicine (University of Pittsburgh)

NEW Postdoctoral Fellowships – Respiratory Biology and Diseases (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Lung Regeneration (AstraZeneca)

Postdoctoral Research Associate – Chronic Lung Disease (Washington University St. Louis)

Faculty Position – Cancer Biology (Wake Forest School of Medicine)

Laboratory Head – Infection & Immunity Division (The Walter and Eliza Hall Institute of Medical Research)

Assistant Professor/Postdoctoral Research Fellow – Lung Injury and Repair (University of Tennessee)

Postdoctoral Opportunity – RNA and Cancer Biology (Yale University)

PhD Student – Asthma Research (Karolinska Institute)

Principal Scientist – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Research Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

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