Dermal Cell News Volume 5.17 | May 13 2019

TOP STORY

Enhanced Dendritic Actin Network Formation in Extended Lamellipodia Drives Proliferation in Growth-Challenged Rac1^P29S Melanoma Cells

Researchers describe how the hyperactivation of Rac1 via the P29S mutation (Rac1^P29S) in melanoma hijacked branched actin network assembly to coordinate proliferative cues that facilitated metastasis and drug resistance. Upon growth challenge, Rac1^P29S-harboring melanoma cells massively upregulated lamellipodia formation by dendritic actin polymerization. [Dev Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Deletion of Exons 17 and 18 in Prestin’s STAS Domain Results in Loss of Function

Investigators sought to delete the intrinsically disordered region to study the functional significance of calcium-dependent, calmodulin binding on outer hair cell function. The hybrid exon that contained the targeted deletion failed to splice in vitro and prestin protein lacking exons 17 and 18 aggregated and failed to target the cell membrane. [Sci Rep] Full Article

Modulation of Coenzyme Q₁₀ Content and Oxidative Status in Human Dermal Fibroblasts Using HMG-CoA Reductase Inhibitor over a Broad Range of Concentrations. From Mitohormesis to Mitochondrial Dysfunction and Accelerated Aging

Researchers showed that pharmacological coenzyme Q₁₀ deprivation at concentrations of statins >10000 nM triggered intracellular oxidative stress, mitochondrial dysfunction and generated cell death in human dermal fibroblasts. On the contrary, at lower statin concentrations, cells and mainly mitochondria, were able to partially adapt and prevent oxidative imbalance and overt mitochondrial toxicity. [Aging (Albany NY)] Full Article

SKIN CANCERS & DISORDERS

The Small GTPase ARF6 Activates PI3K in Melanoma to Induce a Pro-Metastatic State

Investigators showed that constitutive activation of the small GTPase ARF6 was sufficient to accelerate metastasis in mice with BRAFV600E/Cdkn2aNULL melanoma at a similar incidence and severity to Pten loss, a major driver of PI3K activation and melanoma metastasis. [Cancer Res] Abstract

Chromatin Remodellers Brg1 and Bptf Are Required for Normal Gene Expression and Progression of Oncogenic Braf-Driven Mouse Melanoma

Melanocyte identity genes displayed loss of active chromatin marks and RNA polymerase II and gain of heterochromatin marks, indicating epigenetic reprogramming during tumor progression. Nevertheless, late-stage tumor cells grown in culture re-expressed Mitf, and melanocyte markers and Mitf together with Sox10 coregulated a large number of genes essential for their growth. [Cell Death Differ] Abstract

Combined Use of Subclinical Hydroxyurea and CHK1 Inhibitor Effectively Controls Melanoma and Lung Cancer Progression, with Reduced Normal Tissue Toxicity Compared to Gemcitabine

Scientists demonstrated that hydroxyurea effectively synergized with CHK1, but not ATR inhibition, in >70% of melanoma and non-small cell lung cancer cells assessed, resulting in apoptosis and complete loss of proliferative potential in vitro and in vivo. [Mol Oncol] Abstract | Full Article

Gene Expression and Promoter Methylation of Angiogenic and Lymphangiogenic Factors as Prognostic Markers in Melanoma

The authors characterized a linear murine model of melanoma progression and showed that the aggressiveness of melanoma cells was closely associated with high expression of angiogenic factors, such as Vegfc, Angpt2 and Six1, and that blockade of the VEGF pathway by the inhibitor axitinib abrogates their tumorigenic potential in vitro and in the in vivo CAM assay. [Mol Oncol] Abstract | Full Article

JNK2 Is Required for Tumorigenic Properties of Melanoma Cells

Scientists expressed WT and C116S mutants in melanoma cell lines and used c-Jun-N-terminal kinase (JNK)-IN-8 to enable chemical-genetic dissection of JNK1 and JNK2 activity. They found that the JNK2C116S allele consistently enhanced colony proliferation and cell invasiveness in the presence of JNK-IN-8. [ACS Chem Biol] Abstract

Transcriptomic Analysis Reveals Cell Apoptotic Signature Modified by Heparanase in Melanoma Cells

By silencing the heparanase gene (HPSE) in MDA-MB-435s melanoma cells, the authors investigated the impact of this protein on gene transcription. They demonstrated significantly increased apoptotic cells by TUNEL staining upon HPSE silencing, mediated by activation of caspase 3/PARP1 pathway. [J Cell Mol Med] Full Article

The MIF-CD74 Interaction Regulates the Expression of PD-L1 in Melanoma Cells

Immunohistochemical analyses of 97 melanoma tissue samples showed significant correlations between CD74 and the expression status of programmed cell death ligand 1 (PD-L1). In vitro analysis of two melanoma cell lines, which were known to secrete migration inhibitory factor (MIF) constitutively and express cell surface CD74 upon interferon gamma (IFN)-γ stimulation, showed upregulation of PD-L1 levels by IFN-γ stimulation. [Cancer Sci] Abstract

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MicroRNA Dysregulation in Cutaneous Squamous Cell Carcinoma

The authors focus on the recent evidence about the role of miRNAs in the development of cutaneous squamous cell carcinoma and in the prognosis of this form of skin cancer. [Int J Mol Sci] Full Article

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

Vyome Therapeutics Presents Positive Results from Two Key Clinical Trials

Vyome Therapeutics presented positive results from two clinical trials testing its lead anti-acne candidate, VB-1953. [Press release from Vyome Therapeutics, Inc. (GlobeNewswire, Inc.) discussing research presented at the 77^th Annual Meeting of the Society for Investigative Dermatology (SID), Chicago] Press Release

PolarityTE Announces Clinical Data from Two Studies Showing 12-Week Closure of Difficult-to-Treat Lower Extremity Chronic Wounds Using SkinTE

PolarityTE, Inc. announced data from two pilot studies on the use of its SkinTE™ product both showing successful closure of diabetic foot ulcers and venous stasis leg ulcers within a 12-week period. The cases involved patients with lower extremity chronic wounds that were difficult to treat or had failed to heal with standard dressing care and conventional treatments, using a single application of SkinTE. [PolarityTE, Inc.] Press Release

Allakos Announces Positive Results with AK002 in Patients with Severe Allergic Conjunctivitis

Allakos Inc. announced positive Phase I results in patients with severe allergic conjunctivitis. In addition, patients suffering from comorbid atopic dermatitis, asthma and allergic rhinitis, despite treatment with currently available therapies, reported improvements in their symptoms while receiving AK002. [Allakos, Inc.] Press Release

MediWound Enters into Exclusive License Agreement with Vericel for Commercial Rights to NexoBrid^® in North America

MediWound Ltd. announced that it has entered into exclusive license and supply agreements with Vericel Corporation to commercialize NexoBrid^® in North America. [MediWound Ltd.] Press Release

Academics Raise Concerns about Predatory Journals on PubMed

The National Library of Medicine has quality control procedures in place, but some researchers believe additional scrutiny is necessary. [The Scientist] Editorial

Intolerance and Funding Concern Indian Scientists ahead of Election

A rising intolerance towards intellectuals and minority groups in India has prompted scientists there to speak out ahead of the country’s mammoth general election. More than 200 scientists have signed an open letter appealing to citizens to reject the discrimination and violence being promoted by some extremist groups. [Nature News] Editorial

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

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

NEW Postdoctoral Position – Cancer Epigenetics (Harvard University)

NEW Postdoctoral Fellowship – Skin Development, Fibrosis, and Wound Healing (Oklahoma Medical Research Foundation)

NEW Faculty Positions – Allergy, Rheumatology or Skin Biology (University of Rochester)

Postdoctoral Position – Cell Biologist (IUF – Leibniz Research Institute for Environmental Medicine)

Postdoctoral Positions – Cell Competition (University of Bristol)

Faculty Positions – Skin Cancer (Columbia University)

Postdoctoral Research Position – Molecular Biology & Cancer Research (Augusta University)

Postdoctoral Fellowship – Cancer Biology (University of Miami)

Postdoctoral Fellowship – Epidermal Stem Cell Research (University of California, San Diego)

PhD Position – Epidermal Tissue Mechanics (Forschungszentrum Jülich)

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