Dermal Cell News Volume 3.19 | Jun 5 2017

TOP STORY

ALDH1A3 Is Epigenetically Regulated during Melanocyte Transformation and Is a Target for Melanoma Treatment

Using 56 cell lines representing nine different tumor types, the authors demonstrated that melanoma cells exhibited a strong correlation between reactive oxygen species amounts and aldehyde dehydrogenase 1 (ALDH1) activity. They found that ALDH1A3 is upregulated by epigenetic mechanisms in melanoma cells compared with normal melanocytes. [Oncogene] Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

T-Plastin Is Essential for Basement Membrane Assembly and Epidermal Morphogenesis

Investigators identified the actin-bundling protein T-plastin (Pls3) as a regulator of basement membrane assembly and epidermal morphogenesis. In utero depletion of Pls3 transcripts in mouse embryos caused basement membrane and polarity defects in the epidermis but had little effect on cell adhesion and differentiation. Loss-of-function experiments demonstrated that the apicobasal polarity defects were secondary to the disruption of the basement membrane. [Sci Signal] Abstract

Disease-Linked Connexin26 S17F Promotes Volar Skin Abnormalities and Mild Wound Healing Defects in Mice

Several mutant mice have been generated to model connexin (Cx)-linked skin diseases; however, the role of connexins in skin maintenance and during wound healing remains to be fully elucidated. The authors generated a novel, viable, and fertile mouse with the keratitis-ichthyosis-deafness mutant driven by the cytokeratin 14 promoter. This mutant mouse mirrored several Cx26-linked human skin pathologies suggesting that the etiology of Cx26-linked skin disease indeed stems from epidermal expression of the Cx26 mutant. [Cell Death Dis] Full Article

Inhibition of Pathological Phenotype of Hypertrophic Scar Fibroblasts via Co-Culture With Adipose Derived Stem Cells

Investigators evaluated the suppressing effect of adipose derived stem cells (ASCs) on hypertrophic scar (HS) fibroblast bioactivity and the possible mechanism via a co-culture model. [Tissue Eng Part A] Abstract

Growth Factor-Functionalized Silk Membranes Support Wound Healing in Vitro

The authors genetically engineered domesticated silkworm (B. mori) to produce silk functionalized with growth factors to promote wound healing. In this study FGF-, EGF-, KGF-, PDGF- or VEGF-functionalized silk membranes were compared to native B. mori silk membranes without growth factors for their ability to support wound healing. [Biomed Mater] Abstract

SKIN CANCERS & DISORDERS

Nrf2 Promotes Keratinocyte Proliferation in Psoriasis through Up-Regulation of Keratin 6, Keratin 16 and Keratin 17

Researchers investigated whether nuclear factor erythroid-derived 2 related factor 2 (Nrf2) regulates keratinocyte proliferation via promoting expression of K6, K16 and K17 in psoriasis. They found that psoriatic epidermis exhibited elevated expression of Nrf2. Furthermore, Nrf2 promoted expression of K6, K16 and K17 in both HaCaT cells and primary human keratinocytes by binding to the ARE domains located in the promoter of these genes. [J Invest Dermatol] Abstract

The Syk Tyrosine Kinase Is Required for Skin Inflammation in an In Vivo Mouse Model of Epidermolysis Bullosa Acquisita

Scientists identified the Syk tyrosine kinase as a critical component of autoantibody-induced skin inflammation downstream of Src-family kinases. Immobilized type VII collagen (C7)-anti-C7 immune complexes triggered neutrophil activation and Syk phosphorylation in a Src-family kinase-dependent manner. Bone marrow chimeric mice lacking Syk in their hematopoietic compartment were completely protected from skin inflammation triggered by anti-C7 antibodies despite normal circulating anti-C7 levels. [J Invest Dermatol] Abstract

uPA/uPAR System Activation Drives a Glycolytic Phenotype in Melanoma Cells

Researchers showed the involvement of the uPA/uPAR system in the regulation of aerobic glycolysis of melanoma cells. uPAR over-expression in human melanoma cells controls an invasive and glycolytic phenotype in normoxic conditions. [Int J Cancer] Abstract

Photobiomodulation of Human Dermal Fibroblasts In Vitro: Decisive Role of Cell Culture Conditions and Treatment Protocols on Experimental Outcome

Photobiomodulation-based therapies show tantalizing promise for treatment of skin diseases. The authors interrogated the appropriateness of a range of previously-reported treatment parameters, including light wavelength, irradiance and radiant exposure, as well as cell culture conditions (e.g., serum concentration, cell confluency, medium refreshment, direct/indirect treatment, oxygen concentration, etc.), in primary cultures of normal human dermal fibroblasts exposed to visible and near infra-red light. [Sci Rep] Full Article

mTORC1/Autophagy-Regulated MerTK in Mutant BRAFV600 Melanoma with Acquired Resistance to BRAF Inhibition

BRAF inhibitors (BRAFi) and the combination therapy of BRAF and MEK inhibitors were recently approved for therapy of metastatic melanomas harboring the oncogenic BRAFV600 mutation. Although these therapies have shown pronounced therapeutic efficacy, the limited durability of the response indicates an acquired drug resistance that still remains mechanistically poorly understood at the molecular level. Scientists conducted transcriptome gene profiling in BRAFi-treated melanoma cells and identified that Mer tyrosine kinase (MerTK) is specifically upregulated. [Oncotarget] Full Article

LTA4H Regulates Cell Cycle and Skin Carcinogenesis

The authors focused on Leukotriene A4 hydrolase (LTA4H) as a potential target for cancer prevention and/or therapy. They reported that LTA4H is a key regulator of cell cycle at the G0/G1 phase acting by negatively regulating p27 expression in skin cancer. They found that LTA4H is overexpressed in human skin cancer tissue. [Carcinogenesis] Full Article

Molecular and Cytoskeletal Regulations in Epidermal Development

There is increasing evidence suggesting that cytoskeleton-associated proteins, including adhesion proteins and the crosslinker proteins may play critical roles in regulating epidermis development. The authors provide a broad overview of the various molecules involved in epidermal development with special emphasis on the cytoskeletal components. [Semin Cell Dev Biol] Abstract

Implications of Extracellular Matrix Production by Adipose Tissue-Derived Stem Cells for Development of Wound Healing Therapies

Adipose tissue-derived stem cells (ASCs) are recognized to promote wound healing of otherwise chronic wounds, possibly through the reduction of inflammation, induction of angiogenesis, and promotion of fibroblast and keratinocyte growth. Scientists describe the importance of extracellular matrix (ECM) for wound healing, and how ECM production by ASCs may be exploited in developing new therapies for the treatment of chronic wounds. [Int J Mol Sci] Full Article

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

With Nearly Three Years of Follow-Up, KEYTRUDA^® (pembrolizumab) Data Demonstrated Improved Survival Benefit Compared to Ipilimumab in Advanced Melanoma

Merck announced updated longer-term overall survival data from KEYNOTE-006, the phase III study evaluating KEYTRUDA^®, the company’s anti-PD-1 therapy, in patients with unresectable or metastatic melanoma. The data showed sustained superior survival outcomes for patients receiving KEYTRUDA^® compared to ipilimumab in patients who were treatment-naïve or received one prior line of therapy for the treatment of advanced melanoma. [Press release from Merck discussing research presented at American Society of Clinical Oncology (ASCO), Chicago] Press Release

Triple Immunotherapy for Rare Skin Cancer Shows Promise in Small, Early-Stage Trial

Three out of four patients treated with an experimental combination of three different therapies for the rare skin cancer known as Merkel cell carcinoma are in complete remission following the treatment, according to study results from a small clinical trial led at Fred Hutchinson Cancer Research Center. [Press release from Fred Hutchinson Cancer Research Center discussing research presented at American Society of Clinical Oncology (ASCO), Chicago] Press Release

Amicus Therapeutics Receives Rare Pediatric Disease Designation for Sd-101 for Patients with Epidermolysis Bullosa

Amicus Therapeutics, Inc. has received Rare Pediatric Disease designation1 from the U.S. Food and Drug Administration (FDA) for the novel topical medicine SD-101 for the treatment of epidermolysis bullosa (EB). The Rare Pediatric Disease designation for SD-101 covers the broad treatment of EB. [Amicus Therapeutics, Inc.] Press Release

Ralexar Therapeutics Initiates Phase IIb Study of ALX-101 in Patients with Atopic Dermatitis

Ralexar Therapeutics announced that patient enrollment has begun in a Phase IIb clinical study evaluating ALX-101 topical gel as a potential treatment for atopic dermatitis. [Ralexar Therapeutics] Press Release

Castle Creek Pharmaceuticals Announces First Patient Enrolled in DELIVERS Study of Diacerein 1% Ointment for Epidermolysis Bullosa Simplex

Castle Creek Pharmaceuticals announced the first patient has enrolled in the company’s Phase II/III DELIVERS clinical trial evaluating the safety and efficacy of diacerein 1% ointment for the treatment of epidermolysis bullosa simplex. [Castle Creek Pharmaceuticals] Press Release

NIH Plan to Reduce Overhead Payments Draws Fire

President Donald Trump’s administration has brought a long-simmering debate over how the U.S. government supports university research back to a boil. In its 2018 budget proposal, the White House proposes cutting so-called indirect cost payments that the National Institutes of Health (NIH) makes to universities, hospitals, and research institutes by about two-thirds, to 10% of each grant. The administration says the change would allow it to redirect about $4.6 billion now spent each year on overhead—including maintaining labs and complying with regulations—to research. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Wnt Signaling
August 6-11, 2017
Stowe, United States

NEW 3^rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 6-9, 2017
Mainz/Frankfurt, Germany

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

NEW PhD Candidate – Melanoma (University Medical Center Gottingen)

Research Assistant – Melanoma (King’s College London)

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 Program – Melanoma (European Molecular Biology Laboratory)

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

Postdoctoral Position – Wound Healing & Regenerative Medicine (University of Miami)

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