Dermal Cell News Volume 3.20 | Jun 12 2017

TOP STORY

Rare Cell Variability and Drug-Induced Reprogramming as a Mode of Cancer Drug Resistance

Investigators showed that human melanoma cells can display profound transcriptional variability at the single-cell level that predicts which cells will ultimately resist drug treatment. This variability involved infrequent, semi-coordinated transcription of a number of resistance markers at high levels in a very small percentage of cells. [Nature] Abstract | Video

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

WNT10A Mutation Causes Ectodermal Dysplasia by Impairing Progenitor Cell Proliferation and KLF4-Mediated Differentiation

Scientists showed that β-catenin pathway activity and adult epithelial progenitor proliferation were reduced in the absence of WNT10A, and identified Wnt-active self-renewing stem cells in affected tissues including hair follicles, sebaceous glands, taste buds, nails and sweat ducts. [Nat Commun] Full Article | Press Release

Fetal Therapy Model of Myelomeningocele with Three-Dimensional Skin Using Amniotic Fluid Cell-Derived Induced Pluripotent Stem Cells

Scientists performed antenatal treatment of myelomeningocele with an artificial skin using induced pluripotent stem cells (iPSCs) generated from a patient with Down syndrome (AF-T21-iPSCs) and twin-twin transfusion syndrome (AF-TTTS-iPSCs) to a rat model. They manufactured three-dimensional skin with epidermis generated from keratinocytes derived from AF-T21-iPSCs and AF-TTTS-iPSCs and dermis of human fibroblasts and collagen type I. [Stem Cell Reports] Full Article | Press Release

Exploring a Role for Regulatory miRNAs in Wound Healing During Aging: Involvement of miR-200c in Wound Repair

To identify microRNAs negatively impacting the wound repair, researchers performed global miRNA profiling of wounds collected from young and old mice. A subset of miRNAs that exhibited an age-dependent expression pattern during wound closure was identified, including miR-31 and miR-200c. The expression of miR-200 family members was markedly downregulated upon wounding in both young and aged mice, with an exception of acute upregulation of miR-200c at the early phase of wound healing in aged skin. [Sci Rep] Full Article

Direct 3D Cell-Printing of Human Skin with Functional Transwell System

Researchers presented a new 3D cell-printing strategy for engineering a 3D human skin model with a functional transwell system in a single-step process. A hybrid 3D cell-printing system was developed, allowing for the use of extrusion and inkjet modules at the same time. [Biofabrication] Abstract | Press Release

Role of Ambient Gas Composition on Cold Physical Plasma-Elicited Cell Signaling in Keratinocytes

Researchers hypothesized that modulating the environmental plasma conditions from pure nitrogen to pure oxygen in an atmospheric pressure argon plasma jet will change type and concentration of plasma-derived reactive oxygen and nitrogen species and effectively tune the behavior of human skin cells. HaCaT keratinocytes were studied in vitro with regard to cell metabolism, viability, growth, gene expression signature, and cytokine secretion. [Biophys J] Abstract

SKIN CANCERS & DISORDERS

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

Scientists presented a systems-based study of glycomic changes and corresponding enzymes associated with melanoma metastasis in patient samples. Upregulation of core fucosylation (FUT8) and downregulation of α-1,2 fucosylation (FUT1, FUT2) were identified as features of metastatic melanoma. Using both in vitro and in vivo studies, they demonstrated FUT8 was a driver of melanoma metastasis which, when silenced, suppressed invasion and tumor dissemination. [Cancer Cell] Abstract | Graphical Abstract

p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis

Researchers evaluated inhibitors of p90RSK family members: BI-D1870 and BRD7389, for their ability to inhibit both proliferation and protein synthesis in patient-derived melanoma cell lines with acquired resistance to combined treatment with the BRAF inhibitor vemurafenib and MEK inhibitor selumetinib. [J Invest Dermatol] Abstract

IL17A-Dependent Asymmetric Stem Cell Divisions Are Increased in Human Psoriasis; A Mechanism Underlying Benign Hyperproliferation

Scientists hypothesized that the balance between asymmetric SC divisions (ACDs) and symmetric cell divisions (SCDs) would be dysregulated in the benign hyperproliferation of psoriasis. They found that, whereas SCDs were increased in squamous cell carcinoma, ACDs were increased in the benign hyperproliferation of psoriasis. [Stem Cells] Abstract

ROS Production Induced by BRAF Inhibitor Treatment Rewires Metabolic Processes Affecting Cell Growth of Melanoma Cells

Scientists performed time course experiments and a series of western blots in a panel of BRAFV600E and BRAFWT/NRASmut human melanoma cells, which were incubated with BRAF and MEK1 kinase inhibitors. siRNA approaches were used to investigate the metabolic players involved. Reactive oxygen species (ROS) were measured by confocal microscopy and AZD7545, an inhibitor targeting pyruvate dehydrogenase kinase was tested. [Mol Cancer] Full Article

Inhibiting STAT3 Signaling Is Involved in the Anti-Melanoma Effects of a Herbal Formula Comprising Sophorae Flos and Lonicerae Japonicae Flos

The authors investigated whether an ethanolic extract of Sophorae Flos and Lonicerae Japonicae Flos (SLE) exerted anti-melanoma activities by inhibiting signal transducer and activator of transcription 3 (STAT3) signaling. B16F10 allograft model, A375 and B16F10 cells were employed to assess the in vivo and in vitro anti-melanoma activities of SLE. [Sci Rep] Full Article

A New Long Noncoding RNA (LncRNA) Is Induced in Cutaneous Squamous Cell Carcinoma and Downregulates Several Anticancer and Cell-Differentiation Genes in Mouse

The authors demonstrated that the development of mouse tumors induced by the concomitant application of a carcinogen and a tumor promoter (7,12 dimethylbenz[a]anthracene [DMBA] and 12-O-tetradecanoylphorbol-13-acetate [TPA], respectively) was associated with the upregulation of a previously uncharacterized long noncoding RNA, termed AK144841. They found that AK144841 expression was absent from normal skin and was specifically stimulated in tumors and highly tumorigenic cells. [J Biol Chem] Abstract

Melanocytic Nevi and Melanoma: Unraveling a Complex Relationship

Approximately 33% of melanomas are derived directly from benign, melanocytic nevi. Despite this, the vast majority of melanocytic nevi, which typically form as a result of BRAFV600E-activating mutations, will never progress to melanoma. The authors synthesize basic scientific insights and data from mouse models with common observations from clinical practice to comprehensively review melanocytic nevus biology. [Oncogene] Abstract

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

Mallinckrodt Enrolls First Patient in Phase III Trial of StrataGraft^® Regenerative Skin Tissue

Mallinckrodt plc confirmed enrollment of the first patient in the company’s Phase III study assessing the efficacy and safety of StrataGraft regenerative skin tissue in the promotion of autologous skin regeneration of complex skin defects due to thermal burns that contain intact dermal elements. [Mallinckrodt plc] Press Release

Tarix Orphan Granted Orphan Drug Status by the EMA for TXA127 as Potential Treatment for Epidermolysis Bullosa

Tarix Orphan LLC announced that the European Medicines Agency has granted Orphan Drug status to the company’s lead compound, TXA127, for the treatment of epidermolysis bullosa (EB). TXA127 is a pharmaceutical grade formulation of the naturally occurring peptide Angiotensin (1-­7), which Tarix Orphan is developing for the treatment of a number of orphan and genetic diseases, including EB. [Tarix Orphan LLC. (PR Newswire Association LLC.)] Press Release

Foamix Announces Dosing of First Patient in Phase III Rosacea Clinical Trials for FMX103 Minocycline Foam 1.5%

Foamix Pharmaceuticals Ltd. announced that the first patient has been dosed in its Phase III program to evaluate the efficacy and safety of its topical Minocycline Foam 1.5%, FMX103. “The initiation of this Phase III program marks an important milestone for Foamix’s FMX103 and it moves us closer to our goal of providing an effective and convenient new treatment for the millions of patients suffering from moderate-to-severe rosacea,” stated Dr. Dov Tamarkin, CEO of Foamix. [Foamix Pharmaceuticals Ltd.] Press Release

Curiosity and Irritation Meet Macron’s Effort to Lure Foreign Scientists to France

The French government unveiled a website aimed at attracting foreign scientists with four-year grants worth up to €1.5 million each. [ScienceInsider] Editorial

Trump Names Sharpless to Lead U.S. Cancer Institute

President Donald Trump announced his intention to appoint Norman “Ned” Sharpless to be the next director of the National Cancer Institute in Bethesda, Maryland. Sharpless, who is 50 years old, is a physician and currently director of the Lineberger Comprehensive Cancer Center at the University of North Carolina in Chapel Hill. He also holds an academic appointment at the university’s school of medicine. [ScienceInsider] Editorial

NEW European Society for Medical Oncology (ESMO) 2017 Congress
September 8-12, 2017
Madrid, Spain

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

NEW Postdoctoral Research Fellow – Skin Cancer (The University of Queensland)

NEW Postdoctoral Position – Melanoma Drug Resistance and Invasiveness (European Molecular Biology Laboratory)

PhD Candidate – Melanoma (University Medical Center Gottingen)

Postdoctoral Training Fellow – Oncogene Biology (The Francis Crick Institute)

Postdoctoral Position – Skin Cancer and Other Skin Diseases (Boston University)

Assistant Professor – Stem Cell and Regenerative Biology (Harvard University)

Data Scientist – Epithelial Cancer Evolution (Wellcome Trust Sanger Institute)

Postdoctoral Position – Cancer Biology (University of Toronto)

Professorship – Cancer Genomics (Ecole Polytechnique Fédérale de Lausanne)

Postdoctoral Fellow – Skin Stem Cells (Columbia University Medical Center)

Postdoctoral Program – Melanoma (European Molecular Biology Laboratory)

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