Pulmonary Cell News Volume 8.11 | Mar 28 2019

TOP STORY

FBXW2 Suppresses Migration and Invasion of Lung Cancer Cells via Promoting β-Catenin Ubiquitylation and Degradation

Researchers report that FBXW2 is an E3 ligase for β-catenin. FBXW2 bound to β-catenin upon EGF-AKT1-mediated phosphorylation on Ser⁵⁵², and promoted its ubiquitylation and degradation. FBXW2 overexpression inhibited migration and invasion by blocking the transactivation of MMPs driven by β-catenin, whereas FXBW2 knockdown promoted migration, invasion and metastasis both in vitro and in vivo lung cancer models. [Nat Commun] Full Article

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Induction of Inflammatory Responses in Human Bronchial Epithelial Cells by Pb2⁺-Containing Model PM2.5 Particles via Downregulation of a Novel Long Non-Coding RNA lnc-PCK1-2:1

Investigators discovered that carbon nanoparticle-Pb2⁺ adducts, not other pollutants or adducts, induced inflammation in human bronchial cells by suppressing the expression of a novel long non-coding RNA lnc-PCK1-2:1, while lnc-PCK1-2:1 routinely plays a regulatory role in inhibiting inflammation. [Environ Sci Technol] Abstract

Interactions of an Emerging Fungal Pathogen Scedosporium aurantiacum with Human Lung Epithelial Cells

Attachment of conidia of a virulent S. aurantiacum strain onto the human lung epithelial A549 cells in vitro was visualized using microscopy to examine the initial steps of infection. Transcriptomic analysis of the A549 cells revealed that the up-regulated genes were mainly associated with cell repair and inflammatory processes indicating a protective response against S. aurantiacum infection. [Sci Rep] Full Article

LUNG CANCER

PRMT1 Loss Sensitizes Cells to PRMT5 Inhibition

Researchers performed a CRISPR/Cas9 genetic screen in the presence of a PRMT5 inhibitor. Loss of PRMT1, the major asymmetric arginine methyltransferase, sensitized cells to PRMT5 inhibition. They investigated the interplay between PRMT5 and PRMT1, and found that combinatorial inhibitor treatment of small cell lung cancer and pancreatic cancer cell models had a synergistic effect. [Nucleic Acids Res] Full Article

Elevated Heme Synthesis and Uptake Underpin Intensified Oxidative Metabolism and Tumorigenic Functions in Non-Small Cell Lung Cancer Cells

Scientists showed that levels of heme synthesis and uptake, mitochondrial heme, oxygen-utilizing hemoproteins, oxygen consumption, ATP generation, and key mitochondrial biogenesis regulators were enhanced in non-small cell lung cancer cells relative to non-tumorigenic cells. [Cancer Res] Abstract

Distinctive Requirement of PKCε in the Control of Rho GTPases in Epithelial and Mesenchymally Transformed Lung Cancer Cells

Silencing experiments in non-small lung cancer cells revealed that PKCε or other DAG-regulated protein kinase C (PKC) were dispensable for the acquisition of a mesenchymal phenotype induced by transforming growth factor beta (TGF-β). Silencing or inhibiting PKCε enhanced RhoA activity and stress fiber formation, a phenotype also observed in TGF-β-transformed cells. [Oncogene] Abstract

TAZ Sensitizes EGFR Wild-Type Non-Small-Cell Lung Cancer to Gefitinib by Promoting Amphiregulin Transcription

Transcriptional co-activator with the PDZ-binding motif (TAZ) promoted the angiogenesis of non-small-cell lung cancer (NSCLC) cell lines and improved gefitinib sensitivity in epidermal growth factor receptor (EGFR) wild-type NSCLC in vitro and in vivo. Luciferase reporter assays and ChIP-qPCR experiments showed that TAZ upregulated amphiregulin by promoting its transcription. [Cell Death Dis] Full Article

Antrodia cinnamomea Induces Anti-Tumor Activity by Inhibiting the STAT3 Signaling Pathway in Lung Cancer Cells

Antrodia cinnamomea ethanol extract (ACEE) produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma cells. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. [Sci Rep] Full Article

The Kinome of Human Alveolar Type II and Basal Cells, and Its Reprogramming in Lung Cancer

Investigators performed RNA-sequencing on freshly isolated human alveolar type II cells, basal cells, and lung cancer cell lines to define the normal kinome in non-transformed cells and identify kinome changes during transformation. [Am J Respir Cell Mol Biol] Abstract

UPLC-MS-Based Metabolomics Reveals Metabolic Dysregulation in ALDH1A1-Overexpressed Lung Adenocarcinoma Cells

Researchers investigated metabolic alterations induced by aldehyde dehydrogenase 1A1 (ALDH1A1) in lung adenocarcinoma in order to better understand the reprogramming and metabolic mechanism of resistance induced by ALDH1A1. [Metabolomics] Abstract

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer

The authors discuss the key efficacy and safety findings for approved and investigational epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, known mechanisms of resistance, particularly the T790M acquired EGFR mutation, and recent advances in EGFR mutational testing that may facilitate less invasive tissue testing and guide treatment selection. [Expert Rev Anticancer Ther] Abstract

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Breath Diagnostics, Mayo Clinic Laboratories Announce Collaboration to Develop New Diagnostic Test that Detects Lung Cancer Using Patients’ Exhaled Breath

Breath Diagnostics, Inc. and Mayo Clinic Laboratories have announced a collaboration to develop clinical diagnostic tests that use patient breath samples to identify individual biomarkers that can predict a spectrum of diseases. The two organizations will initially focus on a test that can detect lung cancer. [Breath Diagnostics, Inc. (PR Newswire Association LLC.)] Press Release

VUMC and TGen Receive $6.1 Million in Grants to Study Deadly Lung Disease

The Translational Genomics Research Institute (TGen), along with Vanderbilt University Medical Center (VUMC) and the Norton Thoracic Institute at St. Joseph’s Hospital and Medical Center in Arizona, have received a $3.5 million federal grant from the National Institutes of Health to study the cause of idiopathic pulmonary fibrosis, the nation’s most common and severe form of fibrotic lung disease. [Vanderbilt University Medical Center (Newswise, Inc.)] Press Release

Breath Therapeutics Announces Initiation of Global Phase III Trials for the Treatment of Bronchiolitis Obliterans Syndrome

Breath Therapeutics announced the initiation of the Phase III BOSTON clinical studies of liposomal cyclosporine A for inhalation for the treatment of bronchiolitis obliterans syndrome. [Breath Therapeutics] Press Release

Proteostasis Therapeutics Announces Broad New Dataset from Proprietary Combination and Add-On CFTR Modulator Studies in Cystic Fibrosis Patients

Proteostasis Therapeutics, Inc. announced results from Phase I clinical studies of its proprietary cystic fibrosis transmembrane conductance regulator (CFTR) modulators: PTI-801, a third-generation CFTR corrector; PTI-808, a novel CFTR potentiator; and PTI-428, a novel CFTR amplifier. [Proteostasis Therapeutics, Inc.] Press Release

Promedior Received Breakthrough Therapy Designation from FDA for PRM-151 in Idiopathic Pulmonary Fibrosis

Promedior, Inc. announced that PRM-151, a novel investigational anti-fibrotic immunomodulator, has been granted Breakthrough Therapy designation by the FDA for idiopathic pulmonary fibrosis. [Promedior, Inc.] Press Release

Top US Institutes Still Aren’t Reporting Clinical-Trial Results on Time

Many leading US universities are breaking the law by failing to make public the results of clinical trials. A report found that 25 of the 40 universities that sponsor the most trials in the United States did not post study results on a public, government register within twelve months of completion, as is required by US law. [Nature News] Editorial

As Elsevier Falters, Wiley Succeeds in Open-Access Deal Making

Over the last few years, Project DEAL, a consortium that represents around 700 academic institutions in Germany, has been in negotiations for nationwide licensing agreements with three of the largest scholarly publishers—Elsevier, Springer Nature, and Wiley. [The Scientist] Editorial

NEW European Society for Medical Oncology (ESMO) 2019 Congress
September 27-October 1, 2019
Barcelona, Spain

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NEW Postdoctoral Scholar – Acute Respiratory Distress Syndrome (University of California, San Francisco)

NEW Molecular Biologist (Entrinsic Health Solutions, Inc.)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

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

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

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)

Associate Professor – Oncology (University of California, Davis)

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