Dermal Cell News Volume 4.34 | Oct 15 2018

TOP STORY

Remodeling of the Collagen Matrix in Aging Skin Promotes Melanoma Metastasis and Affects Immune Cell Motility

Researchers found that young dermal fibroblasts secreted high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. [Cancer Discov] Abstract | Press Release

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Molecular Characterization and Prospective Isolation of Human Fetal Cochlear Hair Cell Progenitors

Scientists purified postmitotic hair cell progenitors that, when placed in culture in three-dimensional organoids, regained proliferative potential and eventually differentiated to hair cell-like cells in vitro. [Nat Commun] Full Article | Press Release

The Protein Kinase p38α Destabilizes p63 to Limit Epidermal Stem Cell Frequency and Tumorigenic Potential

Researchers found that p38α phosphorylated and thereby destabilized p63, a transcription factor essential for epidermal development. Through this regulatory mechanism, p38α limited the frequency of keratinocytes with stem cell properties and tumorigenic potential. [Sci Signal] Abstract

Amino Acid Substitution in the C-Terminal Domain of Collagen XVII Reduces Laminin-332 Interaction Causing Mild Skin Fragility with Atrophic Scarring

The authors used keratinocytes from patients with junctional epidermolysis bullosa with late onset, which exclusively produced a collagen XVII mutant with the p.R1303Q mutation within its extracellular C-terminus. Although this mutant was normally expressed and targeted to the membrane and the expression of integrins α3β1, α6β4 and of laminin-332 were unchanged, the keratinocytes were less adhesive, showed migratory defects and decreased clonogenic growth. [Matrix Biol] Abstract

Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Accelerate Skin Cell Proliferation

Exosomes were collected from the culture supernatant of mesenchymal stem cells (MSC-exo) and induced MSCs (iMSC-exo), and their characteristics were investigated. Both exosomes enhanced the secretion of collagen in HaCaT and human dermal fibroblasts; however, an increase in fibronectin level was observed only in HaCaT, and this effect was better with iMSC-exo treatment. [Int J Mol Sci] Full Article

SKIN CANCERS & DISORDERS

Tom20 Senses Iron-Activated ROS Signaling to Promote Melanoma Cell Pyroptosis

In melanoma cells, iron enhanced reactive oxygen species (ROS) signaling initiated by carbonyl cyanide m-chlorophenyl hydrazone, causing the oxidation and oligomerization of the mitochondrial outer membrane protein Tom20. Bax was recruited to mitochondria by oxidized Tom20, which facilitated cytochrome c release to cytosol to activate caspase-3, eventually triggering pyroptotic death by inducing gasdermin E cleavage. [Cell Res] Full Article

CDK1 Interacts with Sox2 and Promotes Tumor Initiation in Human Melanoma

Overexpression of CDK1, but not its kinase-dead variant, in melanoma cells increased their spheroid forming ability, tumorigenic potential, and tumor-initiating capacity; inhibition of CDK1 with pharmacological agents reduced these characteristics, which was unexplained by the role of CDK1 in regulating the cell cycle. [Cancer Res] Abstract | Press Release

Overexpression of Desmoglein 2 in a Mouse Model of Gorlin Syndrome Enhances Spontaneous Basal Cell Carcinoma Formation through STAT3-Mediated Gli1 Expression

Overexpression of desmoglein-2 in ASZ001 cells, a Patched1^-/- basal cell carcinoma cell line, induced Stat3 phosphorylation and further increased Gli1 levels, both in an autocrine and paracrine manner. Three different Stat3 inhibitors reduced viability and Gli1 expression in ASZ001 cells, but not in HaCaT cells. [J Invest Dermatol] Abstract

A New ALK Isoform Transported by Extracellular Vesicles Confers Drug Resistance to Melanoma Cells

Investigators report a new mechanism of acquired drug resistance involving the activation of a novel truncated form of anaplastic lymphoma kinase (ALK). Knock down or inhibition of ALK re-sensitised resistant cells to BRAF inhibition and induced apoptosis. [Mol Cancer] Full Article

Yes-Associated Protein Promotes the Abnormal Proliferation of Psoriatic Keratinocytes via an Amphiregulin Dependent Pathway

The authors showed that Yes-associated protein (YAP) expression was elevated in the skin of psoriasis patients and in the Imiquimod mouse model of psoriasis. Knockdown of YAP in HaCaT cells inhibited cell proliferation, caused cell cycle arrest in G0/G1 phase and promoted apoptosis. These changes in YAP-knockdown HaCaT cells were related to changes in amphiregulin expression. [Sci Rep] Full Article

ALDH1 Bio-Activates Nifuroxazide to Eradicate ALDH^High Melanoma-Initiating Cells

Scientists discovered that the 5-nitrofuran, nifuroxazide, was selective for bio-activation by aldehyde dehydrogenase 1 (ALDH1) isoforms over ALDH2, whereby it both oxidized ALDH1 and was converted to cytotoxic metabolites in a two-hit pro-drug mechanism. They showed that ALDH1^High melanoma cells were sensitive to nifuroxazide, while ALDH1A3 loss-of-function mutations confer drug resistance. [Cell Chem Biol] Full Article | Press Release | Graphical Abstract

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Keratin 17 in Disease Pathogenesis: From Cancer to Dermatoses

Investigators review the current understanding of keratin 17 (K17) regulatory mechanism and its pathogenic role in diseases from dermatoses to cancer. Prospects for anti-K17 therapy in diagnosis, prognosis and disease treatment are also discussed. [J Pathol] Abstract | Full Article

Frontiers in Pigment Cell and Melanoma Research

The authors identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. They describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. [Pigment Cell Melanoma Res] Full Article

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

PellePharm Presents Updated Data from Two Phase II Studies Demonstrating the Potential of Patidegib Topical Gel to Treat Basal Cell Carcinomas in Patients with Gorlin Syndrome and in Patients with Non-Gorlin Sporadic BCCs

PellePharm presented updated clinical data from two Phase II studies of patidegib topical gel in a poster session. [Press release from PellePharm (Business Wire, Inc.) discussing research presented at NORD’s Rare Diseases and Orphan Products Breakthrough Summit 2018, Washington, D.C] Press Release

Cronos Group Inc. Partners with Technion Research & Development Foundation for Cannabinoid-Based Skin Care Treatments

Cronos Group Inc. announced that it has entered into a sponsored research agreement with the Technion Research and Development Foundation of the Technion – Israel Institute of Technology to explore the use of cannabinoids and their role in regulating skin health and skin disorders. [The Cronos Group] Press Release

Bausch Health’s BRYHALI^™ (Halobetasol Propionate) Lotion, 0.01%, Receives Tentative FDA Approval for Plaque Psoriasis in Adults

Bausch Health Companies Inc. and its dermatology business, Ortho Dermatologics, announced that the FDA has provided tentative approval of the New Drug Application for BRYHALI^™ lotion for the topical treatment of plaque psoriasis in adult patients. [Bausch Health Companies Inc.] Press Release

Celgene Announces Phase III STYLE Study of OTEZLA^® (Apremilast) in Moderate to Severe Scalp Psoriasis Met Primary Endpoint

Celgene Corporation announced results from the Phase III STYLE study, which showed that OTEZLA^® achieved a highly statistically significant improvement in the primary endpoint of the Scalp Physician’s Global Assessment response at week 16 compared with placebo. [Celgene Corporation] Press Release

BioPharmX Initiates Phase IIb Trial of BPX-04 for Rosacea

BioPharmX Corporation announced that it has enrolled the first subject in a Phase IIb clinical trial of BPX-04, a novel topical gel formulation of minocycline for the treatment of rosacea. [BioPharmX, Inc.] Press Release

Processa Pharmaceuticals Receives FDA Clearance of IND to Begin Phase II Clinical Development of PCS-499 in Necrobiosis Lipoidica Patients

Processa Pharmaceuticals, Inc. announced that the FDA has granted Processa clearance to proceed with a Phase II clinical trial of PCS-499 in patients with necrobiosis lipoidica under a recently submitted Investigational New Drug (IND) application. [Processa Pharmaceuticals] Press Release

Pulse Biosciences Announces Continued Expansion of Its Clinical Study Programs in Dermatology

Pulse Biosciences, Inc. announced the initiation of a clinical feasibility study using its novel Nano-Pulse Stimulation^™ platform to treat patients with cutaneous warts. [Pulse Biosciences, Inc.] Press Release

Mallinckrodt’s Stratatech Company Awarded $26 Million in Additional BARDA Funding for Pediatric Studies of StrataGraft^® Skin Tissue in Thermal Burns

Mallinckrodt plc announced that Stratatech, a Mallinckrodt company, was awarded approximately $26 million in additional Project BioShield funding by the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response. [Mallinckrodt plc (PR Newswire Association LLC.)] Press Release

Report: Former CNRS President Guilty of Fraud

The French Alternative Energies and Atomic Energy Commission has found that cell biologist Anne Peyroche, deputy director of the organization’s Molecular Genetics Laboratory who also served interim president of National Center for Scientific Research, was complicit in the publication of falsified data, according to a report revealed by French news magazine L’Express. [The Scientist] Editorial

The UK Pharmaceutical Industry Braces for Brexit

As Britain’s departure date from the European Union approaches, drugmakers are preparing for potential changes to regulatory procedures and border controls. [The Scientist] Editorial

NEW 24^th World Congress of Dermatology
June 10-15, 2019
Milan, Italy

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

NEW Postdoctoral Position – Translational Skin Cancer Research (German Cancer Research Center DKFZ)

NEW Faculty Investigators – Cancer Research (University of Alabama)

NEW Research Assistant – Tissue Culture/Mammalian Cell Culture (MD Anderson Cancer Center)

Faculty Positions – Cancer Biology (The Wilmot Cancer Institute at the University of Rochester Medical Center)

Tenure Track Group Leader – Mechanisms in Multicellularity or Tissue Regulation (Friedrich Miescher Institure for Biomedical Research)

Group Leader – Organoid Modeling of Disease (European Molecular Laboratory)

Assistant Professor – Department of Biomedical Engineering (Boston University)

Associate Researcher – Inflammatory Skin Diseases (Icahn School of Medicine at Mount Sinai)

Postdoctoral Fellow – Skin Cancer (Stanford University School of Medicine)

PhD or Postdoctoral Position – Tissue Repair, Stem Cell Fate and Tumor Heterogeneity (Université Libre de Bruxelles)

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