Dermal Cell News Volume 3.25 | Jul 24 2017

TOP STORY

Novel CRISPR-Cas9 Genetic Screening Approach Enables Discovery of New Drug Targets to Aid Cancer Immunotherapy

A novel screening method — using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice — has revealed new drug targets that could potentially enhance the effectiveness of PD-1 checkpoint inhibitors, a promising new class of cancer immunotherapy. [Press release from the Dana-Farber Cancer Institute discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Epidermal E-Cadherin Dependent β-Catenin Pathway, is Phytochemical-Inducible and Accelerates Anagen Hair Cycling

The authors used a phytochemical rich in the natural vitamin E tocotrienol (TRF) as a productive tool to unveil a novel epidermal pathway of hair follicular regeneration. Topical TRF application markedly induced epidermal hair follicle development akin to that during fetal skin development. [Mol Ther] Abstract | Graphical Abstract

Angiopoietin-Like 4 Induces a β-Catenin-Mediated Upregulation of ID3 in Fibroblasts to Reduce Scar Collagen Expression

Scientists showed that the matricellular protein, angiopoietin-like 4 (ANGPTL4), accelerated wound closure and reduced collagen expression in diabetic and ANGPTL4-knockout mice. [Sci Rep] Full Article

Skin Renewal Activity of Non-Thermal Plasma through the Activation of β-Catenin in Keratinocytes

Investigators tested the effect of non-thermal plasma (NTP) on the growth of keratinocytes using the HaCaT human keratinocyte cell line and HRM2 hairless mice. Treatment with NTP allowed confluent keratinocytes to escape from G1 cell cycle arrest and increased the proportion of cells in S and G2 phases. [Sci Rep] Full Article

Inhibiting Function of Human Fetal Dermal Mesenchymal Stem Cells on Bioactivities of Keloid Fibroblasts

Scientists showed that fetal dermal mesenchymal stem cells inhibited the bioactivity of eloid fibroblasts (KFs), downregulated the expression of the antiapoptotic protein BCL-2, and upregulated the expression of the proapoptotic protein BAX of KFs by secreting some soluble substances, thus accelerating the apoptosis of KFs. [Stem Cell Res Ther] Full Article

SKIN CANCERS & DISORDERS

An Autophagy-Driven Pathway of ATP Secretion Supports the Aggressive Phenotype of BRAFV600E Inhibitor-Resistant Metastatic Melanoma Cells

Using isogenic human and murine melanoma cell lines of vemurafenib-resistant and patient-derived melanoma cells with primary resistance to the BRAFV600E inhibitor, scientists found that the enhanced migration and invasion of the resistant melanoma cells correlated with an enhanced autophagic capacity and autophagosome-mediated secretion of ATP. [Autophagy] Abstract

BRAF Inhibitors Amplify the Pro-Apoptotic Activity of MEK Inhibitors by Inducing ER Stress in NRAS-Mutant Melanoma

In a previous study, the BRAF inhibitor vemurafenib was shown to induce endoplasmic reticulum stress that together with inhibition of the RAF-MEK-ERK (MAPK) pathway amplified its pro-apoptotic activity in BRAF-mutant melanoma. Scientists investigated whether this effect might extent to NRAS-mutant melanoma, in which MAPK activation would be expected. [Clin Cancer Res] Abstract

PD-L1 Expression and Immune Escape in Melanoma Resistance to MAPK Inhibitors

The authors aimed to examine the relationship between immune activity, PD-L1 expression and tumor cell signaling, in metastatic melanomas prior to and during treatment with targeted MAPK inhibitors. Thirty-eight tumors from 17 patients treated with BRAF inhibitor or combination BRAF/MEK inhibitors with known PD-L1 expression were analyzed. [Clin Cancer Res] Abstract

KMT2A Promotes Melanoma Cell Growth by Targeting HTERT Signaling Pathway

Researchers identified KMT2A as a potential target, which promoted the growth of human melanoma cells. KMT2A knockdown significantly inhibited cell viability and cell migration and induced apoptosis, whereas KMT2A overexpression effectively promoted cell proliferation in various melanoma cell lines. [Cell Death Dis] Full Article

Adaptor Protein p62 Promotes Skin Tumor Growth and Metastasis and Is Induced by UVA Radiation

Using RNA-Seq, researchers showed that UVA induces autophagy and lysosomal gene expression, including the autophagy receptor and substrate p62. They found that UVA activates the transcription factor EB (TFEB), a known regulator of autophagy and lysosomal gene expression, which, in turn, induces p62 transcription. [J Biol Chem] Full Article

Wound Healing in Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a group of inherited diseases characterized by recurrent skin blistering due to impaired epidermal or dermo-epidermal adhesion. In some subtypes, damage to internal organs causes serious comorbidities, and an increased risk of early and aggressive squamous cell carcinoma characterizes recessive dystrophic EB. It is likely that EB will only be cured by mutation-correction interventions, but until that goal becomes a reality we need to pool and extend knowledge about wound management and other strategies to improve quality of life for people with EB. [Br J Dermatol] Abstract

MicroRNA-21 in Skin Fibrosis: Potential for Diagnosis and Treatment

Previous studies have shown that microRNA-21 may play pivotal roles in the regulation of a variety of skin fibrosis, including keloid, scleroderma, and hypertrophic scar. The authors outline the structure, expression, and regulation of microRNA-21 and its role in fibrotic skin diseases. [Mol Diagn Ther] Abstract

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

LEO Pharma Receives Marketing Authorization for Kyntheum^® (Brodalumab), a New Biologic for the Treatment of Moderate-to-Severe Plaque Psoriasis in the European Union

LEO Pharma announced that the European Commission has granted marketing authorization for Kyntheum^®, a new biologic for the treatment of moderate-to-severe plaque psoriasis in adults within the European Union who are candidates for systemic therapy. Kyntheum^® is the first and only biologic that selectively targets the IL-17 receptor subunit A. [Leo Pharma] Press Release

Regeneron and Sanofi Receive Positive Chmp Opinion for Dupixent^® (Dupilumab) to Treat Adult Patients with Moderate-to-Severe Atopic Dermatitis

Regeneron Pharmaceuticals, Inc. and Sanofi announced that the European Medicine Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for the marketing authorization of Dupixent^®, recommending its approval in Europe for use in adults with moderate-to-severe atopic dermatitis who are candidates for systemic therapy. [Regeneron Pharmaceuticals, Inc.] Press Release

U.S. FDA Designates Mallinckrodt’s StrataGraft^® as Regenerative Medicine Advanced Therapy

Mallinckrodt plc announced that StrataGraft^® regenerative skin tissue is among the first products to be designated as a Regenerative Medicine Advanced Therapy by the U.S. Food and Drug Administration under the provisions of the 21st Century Cures Act. [Mallinckrodt plc] Press Release

US Defence Agencies Grapple with Gene Drives

The JASONs, a group of elite scientists that advises the US government on national security, has weighed in on issues ranging from cyber security ​to renewing America’s nuclear arsenal. But at a meeting in June, the secretive group took stock of a new threat: gene drives, a genetic-engineering technology that can swiftly spread modifications through entire populations and could help vanquish malaria-spreading mosquitoes. [Nature News] Editorial

Salk Institute Hit with Discrimination Lawsuit by Third Female Scientist

Following two gender discrimination lawsuits filed last week, a third senior female professor at the Salk Institute for Biological Studies has similarly sued the storied independent institute in San Diego, California. [ScienceInsider] Editorial

NEW 2017 National Cancer Research Institute (NCRI) Cancer Conference
November 5-8, 2017
Liverpool, United Kingdom

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

NEW Postdoctoral Position – Skin Wound Healing and Inflammation (Inserm)

NEW Research Technician – Adult Skin Stem Cells (Howard Hughes Medical Institute)

Postdoctoral Research Associate – Genetic Skin Conditions (King’s College London)

Post-Doc and Research Positions – In Vitro 3D Models of Diseased Skin (University of Minho)

Postdoctoral Fellowship – Epithelial Stem Cell Biology (University of Michigan Healthcare System)

Group Leader – Melanoma (University of Lille Nord de France)

Research Fellow – Melanoma (Dana-Farber Cancer Institute)

Associate Professor – Cancer Biology (NYU Langone School of Medicine)

Postdoctoral Fellow – Vascular-Stromal Regulation in the Dermis (Weill Cornell Medicine)

PhD Candidate – Melanoma (University Medical Center Gottingen)

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