Pulmonary Cell News Volume 8.10 | Mar 21 2019

TOP STORY

Intrinsic Cell-Penetrating Activity Propels Omomyc from Proof of Concept to Viable Anti-MYC Therapy

Investigators showed that the purified Omomyc mini-protein itself spontaneously penetrated into non-small cell lung cancer cells and effectively interfered with MYC transcriptional activity therein. [Sci Transl Med] Abstract

(Ranked by impact factor of the journal)

A Critical Role for miR-142 in Alveolar Epithelial Lineage Formation in Mouse Lung Development

The activation of the glucocorticoid pathway in an in vitro alveolar epithelial lineage differentiation assay led to increased alveolar epithelial type 2 (AT2) marker Sftpc and decreased miR-142 expression. Using miR-142 KO mice, the authors demonstrated an increase in the AT2/AT1 cell number ratio. [Cell Mol Life Sci] Abstract

Activation of mTORC1/PGC1 Axis Promotes Mitochondrial Biogenesis and Induces Cellular Senescence in the Lung Epithelium

Investigators uncovered that the mitochondrial biogenesis pathway driven by the mTOR/PGC1α/β axis is markedly upregulated in senescent lung epithelial cells. Using two different models, they showed that activation of this pathway associates with other features characteristic of enhanced mitochondrial biogenesis, including elevated number of mitochondrion per cell, increased oxidative phosphorylation and augmented mitochondrial ROS production. [Am J Physiol Lung Cell Mol Physiol] Abstract

Pollens Destroy Respiratory Epithelial Cell Anchors and Drive Alphaherpesvirus Infection

The authors demonstrated how pollen proteases of Kentucky bluegrass, white birch and hazel selectively destroy integrity and anchorage of columnar respiratory epithelial cells, but not of basal cells, in both ex vivo respiratory mucosal explants and in vitro primary equine respiratory epithelial cells. [Sci Rep] Full Article

LUNG CANCER

ROR1-CAVIN3 Interaction Required for Caveolae-Dependent Endocytosis and Pro-Survival Signaling in Lung Adenocarcinoma

Researchers found evidence of a mechanistic link between receptor tyrosine kinase-like orphan receptor 1 (ROR1)-CAVIN3 interaction and consequential caveolae trafficking, which was found to utilize a binding site distinct from those for ROR1 interactions with caveolin-1 and CAVIN1, with receptor tyrosine kinase-mediated pro-survival signaling towards AKT in early endosomes in lung adenocarcinoma cells. [Oncogene] Abstract

Combination Therapy of Chloroquine and C₂-Ceramide Enhances Cytotoxicity in Lung Cancer H460 and H1299 Cells

C₂-ceramide exhibited dose-dependent anticancer effects in H460 and H1299 cells and autophagy induction. Zebrafish-based acridine orange staining confirmed the combined effects in vivo. [Cancers] Full Article | Graphical Abstract

Epimagnolin Targeting on an Active Pocket of Mammalian Target of Rapamycin Suppressed Cell Transformation and Colony Growth of Lung Cancer Cells

Scientists observed that epimagnolin, a natural compound abundantly found in Shin-Yi, suppressed cell proliferation by inhibition of epidermal growth factor-induced G1/S cell-cycle phase transition in JB6 Cl41 cells. Epimagnolin efficiently suppressed cell proliferation and anchorage-independent colony growth of H1650, rather than H460, lung cancer cells with dependency of total and phosphorylated protein levels of mTOR and Akt. [Mol Carcinog] Abstract

Dysregulated Redox Regulation Contributes to Nuclear EGFR Localization and Pathogenicity in Lung Cancer

Scientists evaluated whether DUOX1 silencing in lung cancers may be responsible for altered epidermal growth factor receptor (EGFR) regulation. In contrast to normal epithelial cells, EGF stimulation of lung cancer cell lines that lack DUOX1 promoted EGF-induced EGFR internalization and nuclear localization, associated with induction of EGFR-regulated genes and related tumorigenic outcomes. [Sci Rep] Full Article

S100A4 Alters Metabolism and Promotes Invasion of Lung Cancer Cells by Up-Regulating Mitochondrial Complex I Protein NDUFS2

Researchers found that S100 calcium-binding protein A4 (S100A4) or NDUFS2 silencing inhibited mitochondrial complex I activity, reduced cellular ATP level, decreased invasive capacity in 3D growth, and dramatically decreased metastasis rates as well as tumor growth in vivo. [J Biol Chem] Full Article | Abstract

Combination of Hesperetin and Platinum Enhances Anticancer Effect on Lung Adenocarcinoma

Hesperetin suppressed lung adenocarcinoma cell proliferation and migration. The combination treatment of hesperetin with platinum suppressed tumor progression more significantly, especially compared with single drug treatment. [Biomed Pharmacother] Full Article

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Combined Checkpoint Inhibition and Chemotherapy: New Era of 1^st Line Treatment for Non-Small Cell Lung Cancer

Platinum-based chemotherapy has long been the first-line treatment of choice for metastatic non-small-cell lung cancer (NSCLC) patients who lack targetable gene mutations. The arrival of checkpoint blockade has led to a vast shift in the treatment landscape of NSCLC. In this review, the authors focus on the molecular rational for the combination therapy and the results of completed clinical studies. [Mol Ther Oncolytics] Abstract | Full Article

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

New Partnership Between LUNGevity Foundation, Pattern.org, and the Broad Institute Empowers Patients to Be Partners in Research

A new partnership between LUNGevity Foundation, Pattern.org and the Broad Institute of MIT and Harvard will allow lung cancer patients undergoing a surgical resection or a drainage for pleural effusion to direct their excess cancer tissue and fluid samples towards development of next-generation research models. [LUNGevity Foundation] Press Release

Genomics England and Cambridge Cancer Genomics Announce Immunotherapy Partnership

Genomics England and Cambridge Cancer Genomics have announced a broad partnership to improve UK-patient access to immune-system modulating cancer drugs, monitor treatment effectiveness over time, and rapidly identify resistance to these drugs. [Cambridge Cancer Genomics] Press Release

Resverlogix Proudly Announces Funding for Phase II Trial Evaluating Apabetalone in Pulmonary Arterial Hypertension Led by Quebec Heart and Lung Institute – Laval University Researcher

Resverlogix Corp. announced the advancement of a $2.9 million project led by academic collaborators at Quebec Heart and Lung Institute, Laval University, to research the clinical potential of its lead drug apabetalone as a potential therapy for pulmonary arterial hypertension. [Resverlogix Corp.] Press Release

FDA Approves Genentech’s Tecentriq in Combination with Chemotherapy for the Initial Treatment of Adults with Extensive-Stage Small Cell Lung Cancer

Genentech announced that the FDA has approved Tecentriq^®, in combination with carboplatin and etoposide (chemotherapy), for the initial treatment of adults with extensive-stage small cell lung cancer. [Genentech] Press Release

US FDA Grants Saracatinib Orphan Drug Designation for Idiopathic Pulmonary Fibrosis

The FDA has granted Orphan Drug Designation for saracatinib, a potential new medicine for the treatment of idiopathic pulmonary fibrosis, a type of lung disease that results in scarring of the lungs. [AstraZeneca] Press Release

EU’s Biggest Research Program Yet Takes Shape

The European Union’s three governing institutions — the Parliament, Council and Commission — reached agreement in the small hours of 20 March on the outline of the EU’s next seven-year research-funding program. [Nature News] Editorial

Canada Budget Overlooks Basic Research

What a difference a year makes. Canada’s 2019 budget, released on March 19^th, includes modest increases for Prime Minister Justin Trudeau’s government priorities, including neuroscience and genomics research ― nothing like the historic five-year, Can$4-billion boost for basic science and research unveiled in 2018. [Nature News] Editorial

U.S. Researchers Hope Congress Will Dig NSF Out of a $1 Billion Budget Hole

For the second time in three years, President Donald Trump has recommended deep cuts to the National Science Foundation (NSF) in Alexandria, Virginia. And scientists are hoping Congress will again come to the agency’s rescue. [ScienceInsider] Editorial

NEW Gordon Research Conference: Lung Development, Injury and Repair 2019
August 4-9, 2019
Lewiston, Maine, United States

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

NEW Research Associate – Gene Therapy for Cystic Fibrosis (Imperial College London)

NEW Postdoctoral Position – Stem Cells, Regenerative Biology and Medicine (Helmholtz Zentrum München)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Group Leaders – Cardiopulmonary Research (Max Planck Institute for Heart and Lung Research)

Associate Professor – Primary Ciliary Dyskinesia (University of Southampton)

Postdoctoral Fellow – Lung Disease (Icahn School of Medicine at Mount Sinai)

Principal Investigator Positions – Stem Cell Research (The GDL-MP Institute for Stem Cell and Regenerative Biomedicine)

Assistant/Associate/Full Professor – Lung Cancer (University of Cincinnati College of Medicine)

Postdoctoral Position – Lung Biology & Disease (Helmholtz-Center München – German Research Center for Environmental Health)

Postdoctoral Position – Respiratory Research (Monell Chemical Senses Center)

Associate Professor – Oncology (University of California, Davis)

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