Pulmonary Cell News Volume 6.02 | Jan 19 2017

TOP STORY

Ect2-Dependent rRNA Synthesis Is Required for KRAS-TRP53-Driven Lung Adenocarcinoma

Scientists demonstrated that nuclear epithelial cell transforming sequence 2 (Ect2) guanine nucleotide exchange factor activity is required for Kras-Trp53 lung tumorigenesis in vivo and that Ect2-mediated transformation requires Ect2-dependent rDNA transcription. [Cancer Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Deficient Retinoid-Driven Angiogenesis May Contribute to Failure of Adult Human Lung Regeneration in Emphysema

The authors investigated the role of retinoic acid signaling in alveolar epithelial repair with a scratch assay using an alveolar cell line and primary human alveolar type 2 cells from resected lung, and the role in angiogenesis using a tube formation assay with human lung microvascular endothelial cells. [Thorax] Abstract

Controlled Gas Exchange in Whole Lung Bioreactors

Investigators describe the creation, characterization, and validation of a bioreactor system that can control oxygen delivery based on real-time metabolic demand of cultured whole lung tissue. [J Tissue Eng Regen Med] Abstract

In Vitro Uptake and Transport Studies of PEG-PLGA Polymeric Micelles in Respiratory Epithelial Cells

The authors demonstrated that methoxypoly (ethylene glycol) (mPEG)-poly (lactic-co-glycolic acid) (PLGA) micelles translocate human respiratory epithelium in vitro through clathrin-, energy- and cholesterol-mediated endocytosis. [Eur J Pharm Biopharm] Abstract

LUNG CANCER

SMARCA4-Inactivating Mutations Increase Sensitivity to Aurora Kinase a Inhibitor Vx-680 in Non-Small Cell Lung Cancers

Scientists identified AURKA activity as essential in non-small cell lung cancer cells lacking SMARCA4/BRG1. In these cells, RNAi-mediated depletion or chemical inhibition of AURKA induces apoptosis and cell death in vitro and in xenograft mouse models. [Nat Commun] Full Article

The β-TrCP-FBXW2-SKP2 Axis Regulates Lung Cancer Cell Growth with FBXW2 Acting as a Tumor Suppressor

Researchers report that FBXW2, a poorly characterized F-box, is a substrate of β-TrCP1 and an E3 ligase for SKP2. While β-TrCP1 promotes FBXW2 ubiquitylation and shortens its half-life, FBXW2 does the same to SKP2. FBXW2 has tumor suppressor activity against lung cancer cells and blocks oncogenic function of both β-TrCP1 and SKP2. [Nat Commun] Full Article

A Targetable HB-EGF-CITED4 Axis Controls Oncogenesis in Lung Cancer

Scientists found that heparin-binding-epidermal growth factor (HB-EGF), a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells. [Oncogene] Abstract

Targeted Inhibition of EGFR and Glutaminase Induces Metabolic Crisis in EGFR Mutant Lung Cancer

The authors tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. They showed that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase pathway in EGFR lung tumors. [Cell Rep] Full Article | Graphical Abstract

Cell of Origin Links Histotype Spectrum to Immune Microenvironment Diversity in Non-small-Cell Lung Cancer Driven by Mutant Kras and Loss of Lkb1

Investigators studied how the cell of origin contributes to phenotypic heterogeneity following conditional expression of Kras^G12D and loss of Lkb1 (Kras;Lkb1). Using progenitor cell-type-restricted adenoviral Cre to target cells expressing surfactant protein C (SPC) or club cell antigen 10 (CC10), they showed that Ad5-CC10-Cre-infected mice exhibit a shorter latency compared with Ad5-SPC-Cre cohorts. [Cell Rep] Full Article | Graphical Abstract

The Neuropilin 2 Isoform NRP2b Uniquely Supports TGFβ-Mediated Progression in Lung Cancer

Researchers found that in non–small cell lung cancer cell lines, transforming growth factor–β (TGFβ) signaling preferentially increased the abundance of Neuropilins 2b (NRP2b). Although the presence of NRP2b inhibited cultured cell proliferation and primary tumor growth, NRP2b enhanced cellular migration, invasion into Matrigel, and tumorsphere formation in cultured cells in response to TGFβ signaling and promoted metastasis in xenograft mouse models. These effects of overexpressed NRP2b contrast with the effects of overexpressed NRP2a. [Sci Signal] Abstract

Aurora B Expression Modulates Paclitaxel Response in Non-Small Cell Lung Cancer

Taxanes are mitotic poisons widely used in the treatment of non-small cell lung cancer (NSCLC), however, little is known about potential molecular modulators of response to these compounds. Aurora B (AURKB) is a critical regulator of the mitotic spindle assembly, previously shown overexpressed in NSCLC. Scientists investigated the hypothesis that AURKB expression modulates the efficacy of taxanes in NSCLC cells. [Br J Cancer] Abstract

Comparative Analysis of the Mechanical Signals in Lung Development and Compensatory Growth

The author compares the manner in which physical stress imposed on the parenchyma, vasculature and thorax and the thoraco-pulmonary interactions, drive both developmental and compensatory lung growth. [Cell Tissue Res] Abstract

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

€29 Million Research Grant to Assess Risk Posed by Deadly Lung Infections

Experts have received €29 million to investigate serious lung infections that particularly affect babies and older people. Led by Professor Harish Nair at the University of Edinburgh, the respiratory syncytial virus (RSV) Consortium in Europe aims to make a fundamental difference to the understanding and management of RSV. [RSV Consortium in Europe] Press Release

Concert Pharmaceuticals Provides Further Details on CTP-656 Development in U.S. And Europe

Concert Pharmaceuticals, Inc. provided further details on the development plan in the U.S. and Europe for CTP-656, a next generation CFTR potentiator being developed for the treatment of cystic fibrosis. In the U.S., Concert initiated a placebo-controlled Phase II trial to evaluate CTP-656 in cystic fibrosis patients with gating mutations. [Concert Pharmaceuticals, Inc.] Press Release

Gene-Edited Animals Face US Regulatory Crackdown

Researchers transforming animals with the latest genome-engineering tools may be disappointed by draft rules released by the US Food and Drug Administration (FDA). The most controversial of three proposed regulations declares that all animals whose genomes have been intentionally altered will be examined for safety and efficacy in a process similar to that for new drugs. Many researchers had hoped that the FDA would be less stringent about evaluating organisms whose genomes have been edited with precise tools — such as CRISPR and a separate technique called TALENs — than it is for animals that have been given DNA from different species or created using less-sophisticated means. [Nature News] Editorial

Billion-Dollar Project Aims to Prep Vaccines before Epidemics Hit

SARS, Zika, Ebola – when some of the world’s most terrifying disease outbreaks occur, health workers often find themselves powerless. A billion-dollar initiative aims to change that situation by pre-emptively developing and stockpiling vaccines to combat potential epidemic threats. [Nature News] Editorial

NEW Gordon Research Conferences: Physical Science of Cancer
February 5-10, 2017
Galveston, Texas, United States

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

NEW Postdoctoral Position – Cellular Therapeutics in Chronic Lung Disease (Helmholtz Zentrum München)

Postdoctoral Research Scientist – Lung Development and Infectious Disease (University of Texas Health)

Postdoctoral Research Fellow – Lung Cancer (Massachusetts General Hospital)

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

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

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

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