Dermal Cell News 4.23 July 9, 2018 | |
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TOP STORYEZH2-Mediated Primary Cilium Deconstruction Drives Metastatic Melanoma Formation Scientists showed that EZH2 drove tumorigenesis from benign BrafV600E– or NrasQ61K-expressing melanocytes by silencing of genes relevant for the integrity of the primary cilium, a signaling organelle projecting from the surface of vertebrate cells. [Cancer Cell] Abstract | Press Release | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)DERMAL STEM CELLS & TISSUE REGENERATIONKeratinocyte Differentiation Induces APOBEC3A, 3B, and Mitochondrial DNA Hypermutation The authors found that APOBEC3A (A3A) and 3B (A3B) expression, as well as mitochondrial DNA (mtDNA) hypermutation, were induced in a cervical dysplastic cell line W12 when cultured in a differentiating condition. The ectopic expression of A3A or A3B was sufficient to hypermutate mtDNA. [Sci Rep] Full Article Researchers isolated and propagated two equine keratinocyte cultures. Cells were propagated at the rate of 2.39 days/doubling for more than 40 population doublings. A feeder-free culture method was also developed for long-term expansion. PCR and FISH validated equine-specific markers in the cultures. [Stem Cell Res Ther] Full Article Photobiomodulation Therapy Promotes In Vitro Wound Healing in Nicastrin KO HaCaT Cells Photobiomodulation (PBM) exerted a potent action on the metabolism of mutated keratinocytes, incrementing ATP production at 2‐hours, while after 24‐hours an increase of metabolism with a decrement of intracellular ATP levels were recorded. Moreover, PBM sped up wound closure, inducing cell migration without affecting their proliferation. [J Biophotonics] Abstract Acute cobalt chloride (CoCl2) exposure markedly increased the levels of intracellular reactive oxygen species and resulted in hypoxic damage and cytotoxicity of HaCaT cells. Stable knockdown of nuclear factor E2-related factor 2 (NRF2) dramatically reduced the expression of many antioxidant enzymes and sensitized the cells to acute CoCl2-induced oxidative stress and cytotoxicity. [Toxicol Appl Pharmacol] Abstract Comparing the samples from fibroblasts cultured with cyclosporin A and those cultured without, up-regulated changes of CYP19A1, 1B1, 7A1, 7F1, 17A1 and down-regulated 2D6 gene expression were observed. All distinguished cytochrome P450 genes (CYPs) encode monooxygenases, which play an important role in steroid biosynthesis and metabolism. [Molecules] Full Article SKIN CANCERS & DISORDERSBi-Allelic Loss of CDKN2A Initiates Melanoma Invasion via BRN2 Activation Scientists discovered that a lineage-restricted transcription factor, BRN2, is downstream of CDKN2A and directly regulated by E2F1. Loss of the CDKN2A protein product p16INK4A permitted metastatic dissemination of human melanoma lines in mice, a phenotype rescued by inhibition of BRN2. [Cancer Cell] Abstract | Press Release | Graphical Abstract Card14−/− mice displayed attenuated skin inflammation in the imiquimod-induced psoriasis model due to impaired IL-17A signaling in keratinocytes. CARMA2, mainly expressed in keratinocytes, associated with the ACT1-TRAF6 signaling complex and mediated IL-17A-induced NF-κB and MAPK signaling pathway activation, which led to expression of pro-inflammatory factors. [Immunity] Abstract | Graphical Abstract The authors indicated that cyclobutane pyrimidine dimer (CPD) lesions were elevated at active transcription factor binding sites (TFBS), an effect that was primarily due to E26 transformation-specific (ETS) TFs. They showed that ETS TFs induced a unique signature of CPD hotspots that were highly correlated with recurrent mutations in melanomas, despite high repair activity at these sites. [Nat Commun] Full Article Gentamicin-induced laminin β3 led to the restoration of laminin 332 assembly, secretion, and deposition within the dermal/epidermal junction, as well as proper polarization of α6β4 integrin in basal keratinocytes, as assessed by immunoblot analysis, immunofluorescent microscopy, and an in vitro 3D skin equivalent model. [Proc Natl Acad Sci USA] Abstract Investigators designed five guide RNAs to correct a recessive dystrophic epidermolysis bullosa (RDEB) causative null mutation in exon 2. Among the site-specific guide RNAs tested, one showed significant cleavage activity in primary RDEB keratinocytes and in fibroblasts when delivered as integration-deficient lentivirus. [Mol Ther] Abstract Marked Global DNA Hypomethylation Is Associated with Constitutive PD-L1 Expression in Melanoma Researchers showed that loss of global DNA methylation, particularly in intergenic regions and repeat elements, was associated with constitutive, versus inducible, PD-L1 expression in melanoma cell lines. This was accompanied by transcriptomic up-regulation. De novo epigenetic regulators were strongly correlated with PD-L1 expression and methylome status. [iScience] Full Article Subscribe to one of our other 19 science newsletters such as Extracellular Matrix News & Cancer Stem Cell News. | |
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REVIEWSFoxn1 in Skin Development, Homeostasis and Wound Healing The authors focus on the transcription factor Foxn1 and its role in skin biology. In particular, the pivotal role of Foxn1 in skin development and the acquisition of the adult skin phenotype, which coincides with losing the ability of scar-free healing, is discussed. [Int J Mol Sci] Full Article | Graphical Abstract Roles of the Glucocorticoid and Mineralocorticoid Receptors in Skin Pathophysiology The combined loss of epidermal glucocorticoid (GC) receptors (GRs) and mineralocorticoid receptors (MRs) cause a more severe skin phenotype relative to single knock-outs in developing skin and in acute inflammation and psoriasis, indicating that these corticosteroid receptors play cooperative roles. Understanding GR- and MR-mediated signaling in skin should contribute to deciphering their tissue-specific relative roles and ultimately help to improve GC-based therapies. [Int J Mol Sci] Full Article | Graphical Abstract Visit our reviews page to see a complete list of reviews in the dermal cell research field. | |
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INDUSTRY NEWSCellect Signs Collaboration Agreement with Dresden University denovoMATRIX Team According to the agreement, the team of denovoMATRIX employed by Technische Universität Dresden will conduct examinations into the tentative synergy between Cellect’s ApoGraft™ and the denovoMAtrix technology for the purpose of evaluating collaborative development of products for regenerative medicine. [Cellect Biotherapeutics Ltd.] Press Release Array BioPharma Inc. announced that the U.S. FDA has approved BRAFTOVI™ capsules in combination with MEKTOVI® tablets for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAFV600K mutation, as detected by an FDA-approved test. BRAFTOVI is not indicated for the treatment of patients with wild-type BRAF melanoma. [Array BioPharma] Press Release Bristol-Myers Squibb Company announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended expanded approval of the current indications for Opdivo to include the adjuvant treatment of adult patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection. [Bristol-Myers Squibb Company] Press Release Sarah Cannon Research Institute – UK Offers TIL Therapy to Patients with Metastatic Melanoma Sarah Cannon Research Institute – UK, announced the European initiation of a Phase II clinical trial studying the effectiveness of TIL therapy in the treatment of patients facing metastatic melanoma. Sarah Cannon is the first clinical site in Europe to treat a patient on this trial. [C-HCA, Inc.] Press Release Histogen Kicks Off Clinical Trial for Female Hair Loss Histogen, Inc., has launched a Phase I clinical trial of its lead product, Hair Stimulating Complex, to treat female diffuse hair loss. This follows approval of the company’s Investigational New Drug application by the US FDA. [Histogen Inc.] Press Release CollPlant announced that it has received grant approval from the Israel Innovation Authority to finance continued development of the Company’s proprietary rhCollagen-based formulations intended for use as BioInk for the 3D printing of tissues and life savings organs. [CollPlant Ltd.] Press Release | |
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POLICY NEWSGermany’s Prestigious Max Planck Society Investigates New Allegations of Abuse The Max Planck Society, one of Germany’s wealthiest and most prestigious research organizations, is investigating fresh allegations of bullying and sexual harassment following an anonymous survey at one of its institutes. [Nature News] Editorial New Scheme for Overseas Researchers to Come to the UK The new ‘UKRI Science, Research and Academia’ scheme, which allows non-EEA researchers, scientists and academics to come to the UK for up to 2 years, opens Friday 6 July, the Immigration Minister has announced. [GOV.UK] Editorial The country is making a serious investment in becoming a world-class science superpower. [Scientific American] Editorial Hidden Conflicts? Pharma Payments to FDA Advisers after Drug Approvals Spark Ethical Concerns In examining compensation records from drug companies to physicians who advised FDA on whether to approve 28 psychopharmacologic, arthritis, and cardiac or renal drugs between 2008 and 2014, Science found widespread after-the-fact payments or research support to panel members. The agency’s safeguards against potential conflicts of interest are not designed to prevent such future financial ties. [ScienceInsider] Editorial
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EVENTSNEW The American Society for Cell Biology (ASCB) Annual Meeting 2018 Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESPostdoctoral Research Fellow – Skin Cancer Biology (The University of Colorado) Postdoctoral Researcher – Stem Cell & Regenerative Medicine (NYU Langone Medical Center) NEW Head of Human Clinical Development – Oncology & Wound Healing (QBiotics Group Limited) Assistant, Associate or Full Professor – Regenerative Medicine (University of San Diego) Associate Professor or Professor – Skin Cancer (The University of Texas M.D. Anderson Cancer Center) Postdoctoral Fellow – Psoriasis Research (Case Western Reserve University) Postdoctoral Researcher – Melanoma (Ghent University) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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