Pulmonary Cell News Volume 8.25 | Jul 4 2019

TOP STORY

Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1

Investigators showed that heme triggered the degradation of Bach1, a pro-metastatic transcription factor, by promoting its interaction with the ubiquitin ligase Fbxo22. Nrf2 accumulation in lung cancers caused the stabilization of Bach1 by inducing Ho1, the enzyme catabolizing heme. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Melatonin Prevents Lung Injury by Regulating Apelin 13 to Improve Mitochondrial Dysfunction

Scientists found that melatonin significantly decreased mortality and restored the function of the alveolar epithelium in bleomycin-treated mice. However, pulmonary function mainly depended on type II alveolar epithelial cells and was linked to mitochondrial integrity. [Exp Mol Med] Full Article

Manganese Uptake by A549 Cells is Mediated by Both ZIP8 and ZIP14

Using siRNA technology, investigators identified Zrt- and Irt-like protein (ZIP)8 and ZIP14 as the major transporters mediating manganese uptake by A549 cells. [Nutrients] Full Article

LUNG CANCER

BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis

Researchers showed that long-term supplementation with the antioxidants N-acetylcysteine and vitamin E promoted KRAS-driven lung cancer metastasis. The antioxidants stimulated metastasis by reducing levels of free heme and stabilizing the transcription factor BACH1. [Cell] Abstract | Press Release | Graphical Abstract

The Deubiquitylase OTUD3 Stabilizes GRP78 and Promotes Lung Tumorigenesis

The authors demonstrated that in vivo deletion of OTUD3 promoted breast cancer development in mice, but by contrast, it slowed down Kras^G12D-driven lung adenocarcinoma initiation and progression and markedly increased survival in mice. [Nat Commun] Full Article

The Dual PI3K/mTOR Inhibitor BEZ235 Restricts the Growth of Lung Cancer Tumors Regardless of EGFR Status, as a Potent Accompanist in Combined Therapeutic Regimens

BEZ235 suppressed tumor growth in vitro and in vivo by inducing cell-cycle arrest at G1 phase, but without causing cell death. It also reduced the expression of cyclin D1/D3 by regulating both its transcription and protein stability. [J Exp Clin Cancer Res] Full Article

LSH Interacts with and Stabilizes GINS4 Transcript that Promotes Tumourigenesis in Non-Small Cell Lung Cancer

GINS4 promoted many characteristics of tumorigenesis including cell growth, clonal formation, migration and invasion, epithelial-mesenchymal transition, tumor sphere and tumor growth in vivo. [J Exp Clin Cancer Res] Full Article

IL-32γ Suppresses Lung Cancer Stem Cell Growth via Inhibition of ITGAV-Mediated STAT5 Pathway

IL-32γ suppressed CD133⁺ cancer stem cell (CSC)-induced allograft model in IL-32γ Tg mice and xenograft model. Tumor-sphere formation and cell viability assay revealed a greater inhibition of CSC proliferation and antineoplastic activity of IL-32γ in CD133⁺ CSCs as compared with normal cancer cells. [Cell Death Dis] Full Article

The HtrA3 Protease Promotes Drug-Induced Death of Lung Cancer Cells by Cleavage of the X-Linked Inhibitor of Apoptosis Protein (XIAP)

Exogenous ΔN-HtrA3L/S promoted apoptotic death of lung cancer cells treated with etoposide and caused a significant decrease of cellular XIAP levels, in a way dependent on HtrA3 proteolytic activity. [FEBS J] Abstract

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Intrinsic Resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance

Scientists describe the identified mechanisms connected with intrinsic EGFR-tyrosine-kinase-inhibitor (TKI)-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, they highlight the need for extensive pre-treatment molecular profiling of advanced non-small cell lung cancer for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them. [Cancers] Full Article

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Calithera Biosciences Initiates Phase I/II Trial of Telaglenastat in Combination with Pfizer’s CDK4/6 Inhibitor Palbociclib

Calithera Biosciences, Inc. announced treatment of the first patient in a Phase I/II open-label clinical trial of the glutaminase inhibitor telaglenastat in combination with Pfizer’s CDK 4/6 inhibitor palbociclib, also known as Ibrance^®. [Calithera Biosciences, Inc.] Press Release

Aridis Pharmaceuticals Receives Orphan Drug Designation for AR-501

Aridis Pharmaceuticals, Inc. announced that the FDA has granted orphan drug designation to AR-501, the company’s inhaled formulation of gallium citrate for treatment of lung infection in patients with CF. [Aridis Pharmaceuticals, Inc.] Press Release

Why India Is Striking Back against Predatory Journals

According to 2015 estimates, more than 8,000 predatory journals churn out more than 400,000 items a year, and India — which has also seen a spurt in high-quality scientific publications – contributes more than one-third of the articles in predatory publications. Last month, India launched its latest salvo against the ‘pay and publish trash’ culture that sustains predatory journals. [Nature News] Editorial

FDA Enforcement Actions Plummet under Trump

From monitoring clinical trials and approving medicines and vaccines, to ensuring the safety of blood transfusions, medical devices, groceries, and more, the FDA is one of the nation’s most vital watchdogs. By several measures, however, FDA’s compliance and enforcement actions have plummeted since President Donald Trump took office, Science has found. [ScienceInsider] Editorial

NEW Fibrosis and Tissue Repair: From Molecules and Mechanics to Therapeutic Approaches
February 19-23, 2020
Victoria, British Columbia, Canada

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NEW PhD Studentship – Extracellular Vesicles in Pulmonary Fibrosis (Université de Franche-Comté)

NEW Postdoctoral Position – Lung Injury (University of Connecticut)

Scientist – Pulmonary (STEMCELL Technologies Inc.)

Postdoctoral Fellowship – Redox Biology of Lung and Breast Cancer (Washington University School of Medicine)

Postdoctoral Fellow – Pluripotent Stem Cell-Derived Human Lung Organoids (Columbia University Irving Medical Center)

Researcher Position – Translational Cancer Research (University of Tromsø)

Postdoctoral Researcher – Cystic Fibrosis Stem Cell Models (The University of Alabama at Birmingham)

Postdoctoral Researcher – Lung Lineage Development (Hospital for Sick Children)

Assistant Professor – Lung Disease Research (University of McGill)

Postdoctoral Fellowship – RNA in Lung Sepsis and Inflammation (Boston University)

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