Pulmonary Cell News Volume 5.38 | Sep 29 2016

TOP STORY

XPO1-Dependent Nuclear Export Is a Druggable Vulnerability in KRAS-Mutant Lung Cancer

Researchers demonstrated the acute and specific cell-autonomous addiction of KRAS-mutant non-small-cell lung cancer cells to receptor-dependent nuclear export. A multi-genomic, data-driven approach, utilizing 106 human non-small-cell lung cancer cell lines, was used to interrogate 4,725 biological processes with 39,760 short interfering RNA pools for those selectively required for the survival of KRAS-mutant cells that harbour a broad spectrum of phenotypic variation. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Activation of MTOR in Pulmonary Epithelium Promotes LPS-Induced Acute Lung Injury

Scientists observed that lipopolysaccharide stimulation induced mechanistic target of rapamycin [serine/threonine kinase] (MTOR) phosphorylation and decreased the expression of microtubule-associated protein 1 light chain 3 beta-II, a hallmark of autophagy, in mouse lung epithelium and in human bronchial epithelial (HBE) cells. The activation of MTOR in HBE cells was mediated by toll-like receptor 4 signaling. [Autophagy] Abstract

A Bioengineered Niche Promotes In Vivo Engraftment and Maturation of Pluripotent Stem Cell Derived Human Lung Organoids

Researchers showed that human lung organoids (HLOs) required a bioartificial microporous Poly(lactide-co-glycolide) scaffold niche for successful engraftment, long-term survival, and maturation of lung epithelium in vivo. Analysis of scaffold-grown transplanted tissue showed airway-like tissue with enhanced epithelial structure and organization compared to HLOs grown in vitro. [ELife] Full Article

Distal Airway Epithelial Progenitor Cells Are Radiosensitive to High-LET Radiation

Investigators showed that exposure to high-linear energy transfer (LET) radiation led to a prolonged loss of in vitro colony forming ability by airway epithelial progenitor cells. [Sci Rep] Full Article

Human Lung Spheroids as In Vitro Niches of Lung Progenitor Cells with Distinctive Paracrine and Plasticity Properties

Scientists aimed at understanding how different cell culture conditions may affect, in vitro, the phenotype of lung progenitor cells to create an ideal niche-like microenvironment. [Stem Cells Transl Med] Abstract

LUNG CANCER

Role of KEAP1/NRF2 and TP53 Mutations in Lung Squamous Cell Carcinoma Development and Radiation Resistance

Scientists described novel murine lung squamous cell carcinoma (LSCC) models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. [Cancer Discov] Abstract

Identification of TRA2B-DNAH5 Fusion as a Novel Oncogenic Driver in Human Lung Squamous Cell Carcinoma

Investigators identified the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung squamous cell carcinoma. [Cell Res] Abstract

The Tobacco-Specific Carcinogen-Operated Calcium Channel Promotes Lung Tumorigenesis via IGF2 Exocytosis in Lung Epithelial Cells

The authors investigated the role of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-mediated Ca²⁺ signaling in lung cancer formation. They showed significant overexpression of insulin-like growth factors (IGFs) in association with IGF-1R activation in human preneoplastic lung lesions in smokers. [Nat Commun] Full Article

Hsa-miR-623 Suppresses Tumor Progression in Human Lung Adenocarcinoma

Investigators found that hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. [Cell Death Dis] Full Article

Short-Term EGFR Blockade Enhances Immune-Mediated Cytotoxicity of EGFR Mutant Lung Cancer Cells: Rationale for Combination Therapies

Scientists showed that short-term exposure of tumor cells to low-dose erlotinib modulates tumor plasticity and immune-mediated cytotoxicity in lung cancer cells harboring a sensitizing epidermal growth factor receptor (EGFR) mutation, leading to a remarkable enhancement of tumor lysis mediated by innate NK cells and antigen-specific T cells. [Cell Death Dis] Full Article

Decreased Glutathione Biosynthesis Contributes to EGFR T790M-Driven Erlotinib Resistance in Non-Small Cell Lung Cancer

The authors analyzed the metabonomic differences between two independent pairs of erlotinib-sensitive/resistant cells and discovered that glutathione (GSH) levels were significantly reduced in T790M epidermal growth factor receptor cells. They also found that increasing GSH levels in erlotinib-resistant cells re-sensitised them, whereas reducing GSH levels in erlotinib-sensitive cells made them resistant. [Cell Discov] Full Article | Press Release

Maintaining Cell Identity: PRC2-Mediated Regulation of Transcription and Cancer

Several observations show that PRC2 can have both oncogenic and tumor-suppressive functions. The authors propose that these apparently opposing roles of Polycomb repressive complex 2 (PRC2) in cancer are a consequence of the molecular function of the complex in maintaining, rather than specifying, the transcriptional repression state of its several thousand target genes. [Nat Rev Cancer] Abstract

Altered Metabolite Levels in Cancer: Implications for Tumor Biology and Cancer Therapy

The authors discuss the mechanisms that lead to changes in metabolite concentrations in cancer cells, the consequences of these changes for the cells and how they might be exploited to improve cancer therapy. [Nat Rev Cancer] Abstract

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

Hypofractionated Radiation Therapy Can Halve Treatment Time for Poor Performance Status Lung Cancer Patients

The American Society for Radiation Oncology announced that survival rates from accelerated treatment equivalent to conventional radiation therapy with limited severe toxicities for poor performance status stage II and III non-small cell lung cancer patients. [Press release from the American Society for Radiation Oncology discussing research presented at the 58^th Annual Meeting of the American Society for Radiation Oncology (ASTRO), Boston] Press Release

Spyryx Biosciences to Present at Jefferies Cystic Fibrosis Summit

Spyryx Biosciences announced that John Taylor will provide an update on the Company’s corporate progress and clinical activities focused on SPX-101, a SPLUNC1-derived peptide shown pre-clinically to modulate a natural pathway that plays an important role in regulating airway surface liquid in the human lung, which is of particular interest in cystic fibrosis. [Press release from Spyryx Biosciences (PR Newswire Association LLC.) discussing research presented at the Jefferies Cystic Fibrosis Summit, New York] Press Release

Boehringer Ingelheim and BioMed X Apply Crowdsourcing to Establish a Team of Scientists for Identifying Key Epigenetic Regulators of COPD

Boehringer Ingelheim and BioMed X announced that they have successfully applied a crowdsourcing approach to establish a research team of outstanding scientists from around the world with bright ideas, who will endeavor to identify new approaches for the treatment of patients with chronic obstructive pulmonary disease (COPD). [Boehringer Ingelheim] Press Release

Boehringer Ingelheim and Sarah Cannon Research Institute Launch Strategic Collaboration to Develop Novel Immune-Oncology Therapies

Boehringer Ingelheim and Sarah Cannon Research Institute announced a new strategic collaboration. The joint clinical development programme will study Boehringer Ingelheim’s BI 754091 and BI 754111 monoclonal antibodies for the combination treatment of multiple cancers with high unmet medical needs, including non-small cell lung cancer. [Boehringer Ingelheim] Press Release

BeyondSpring Announces First Patient Enrolled in Phase Ib/II Investigator-Initiated Trial of Plinabulin plus Nivolumab for Non-Small Cell Lung Cancer

BeyondSpring Pharmaceuticals announced that the first patient in the Phase Ib/II trial of its lead immuno-oncology asset Plinabulin in combination with Nivolumab, an immune-checkpoint inhibitor, in patients with metastatic non-small cell lung cancer was enrolled. [BeyondSpring Pharmaceuticals] Press Release

Science Spending Boosted in French Budget

France’s government has proposed an unusually generous boost to research and higher education in its 2017 draft budget. “This is the largest increase for 15 years,” Thierry Mandon, France’s research and higher-education minister, told reporters at a press conference. [Nature News] Editorial

Open-Access Journal eLife to Start Charging Fees

The open-access journal eLife is dropping one of its most distinctive features: free publishing. From 2017, it will charge a fee of $2,500 for all accepted papers. [Nature News] Editorial

Can Cuban Science Go Global?

Tensions between Cuba and the United States are easing. But researchers still struggle to join the scientific world. [Nature News] Editorial

Validate Your Antibodies to Improve Reproducibility? Easier Said Than Done

More than 100 researchers, antibody manufacturers, journal editors, and funders met in Pacific Grove, California, to hash out standardized approaches to antibody testing. [Science Insider] Editorial

NEW Advances in Cell Engineering, Imaging and Screening
November 17-18, 2016
Leuven, Belgium

NEW Stem Cells and Regenerative Medicine 2^nd International Congress
April 19-21, 2017
Mashhad, Iran

NEW The Biology of Regenerative Medicine
April 25-27, 2017
Hinxton, United Kingdom

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

NEW Professor Position – Pulmonary Cell Research (University of Pennsylvania)

Postdoctoral Research Fellowship – Lung Disease (Johns Hopkins University)

Postdoctoral Fellow – Regenerative Medicine/Biomedical Science (University of California)

Scientist/Senior Scientist – Nanoparticle Research and Drug Delivery (Moderna Therapeutics)

Chair in Medical Biology – Head of the Department of Biology (Masaryk University)

Postdoctoral Fellow – Directed Differentiation of Human Pluripotent Stem Cells into Lung and Airway Epithelial Cells (Columbia University Medical Center)

Tenure-Track Faculty Positions – Inflammation and Inflammatory Lung Diseases (Temple University)

Postdoctoral Research Fellowship – Translational Fibrosis Research (RWTH Aachen University)

Postdoctoral Fellow – Cell and Animal Models of Lung Cancer (University of Kentucky Markey Cancer Center)

Non-Clinical Lecturer – Reader in Respiratory Science (Imperial College London)

Director Clinical Research – Medical Oncology (Fred Hutchinson Cancer Research Center)

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