Dermal Cell News Volume 3.05 | Feb 20 2017

TOP STORY

Regeneration of Fat Cells from Myofibroblasts during Wound Healing

The authors discovered in the mouse that during wound healing, adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and nonadipogenic. Adipocytes formed from human keloid fibroblasts either when treated with bone morphogenetic protein or when placed with human hair follicles in vitro. [Science] Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

A Novel DLX3–PKC Integrated Signaling Network Drives Keratinocyte Differentiation

Researchers showed that DLX3 expression and its downstream signaling depend on protein kinase C (PKC) α activity in skin. They found that following 12-O-tetradecanoyl-phorbol-13-acetate topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKCα by transgenic targeting, resulting in cell cycle block and terminal differentiation. [Cell Death Differ] Full Article

Protective Role of Mitochondrial Peroxiredoxin III against UVB-Induced Apoptosis of Epidermal Keratinocytes

The protective role of peroxiredoxin III (PrxIII) against ultraviolet B (UVB)-induced apoptosis of epidermal keratinocytes was investigated. Mitochondrial H₂O₂ levels were differentiated from other types of reactive oxygen species using mitochondria-specific fluorescent H₂O₂ indicators. Upon UVB irradiation, PrxIII-knockdown HaCaT human keratinocytes and PrxIII-deficient mouse primary keratinocytes exhibited enhanced accumulation of mitochondrial H₂O₂ compared to PrxIII-expressing controls. [J Invest Dermatol] Abstract

Effects of Human Mesenchymal Stem Cells Co-Culture on Calcium-Induced Differentiation of Normal Human Keratinocytes

Scientists co-cultured umbilical cord blood-derived mesenchymal stem cells (MSCs) with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca²⁺) concentration. They found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca²⁺ environment in TGFβ1-dependent manner. [Stem Cells] Abstract

SKIN CANCERS & DISORDERS

Usp9x Regulates Ets-1 Ubiquitination and Stability to Control NRAS Expression and Tumorigenicity in Melanoma

Investigators report that Ets-1 destruction was regulated by the deubiquitinating enzyme, Usp9x, and had major impact on the tumorigenic program of metastatic melanoma. Ets-1 deubiquitination blocked its proteasomal destruction and enhanced tumorigenicity, which could be reversed by Usp9x knockdown or inhibition. [Nat Commun] Full Article

Microenvironment-Derived Factors Driving Metastatic Plasticity in Melanoma

Since MITF induces pigmentation, scientists hypothesized that macrometastatic success should be favored by microenvironments that induce a MITF^HI/differentiated/proliferative state. Zebrafish imaging demonstrated that after extravasation, melanoma cells became pigmented and enacted a gene expression program of melanocyte differentiation. [Nat Commun] Full Article

Myeloid Cells That Impair Immunotherapy Are Restored in Melanomas Which Acquire Resistance to BRAF Inhibitors

Researchers provided preclinical evidence that resistance to BRAFV600E inhibitors (BRAFi) in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment. In contrast to restoration of MDSC, levels of T regulatory cells remained reduced in BRAFi-resistant tumors. [Cancer Res] Abstract

Melanocyte Transformation Requires Complete Loss of All Pocket Protein Function via a Mechanism That Mitigates the Need for MAPK Pathway Activation

Cohorts of mice carrying melanocyte-specific knockouts of various combinations of the three pocket proteins (PPs) were generated. Mice null for pRb, p107, p130 or any combination of double mutants did not develop melanoma. Melanocyte-specific loss of all three PPs facilitated melanoma development. Tumorigenesis was exacerbated by Trp53 co-deletion, with cell culture studies indicating that this difference may result from the apoptotic role of Trp53. [Oncogene] Abstract

Integration of microRNA and mRNA Expression Profiles in the Skin of Systemic Sclerosis Patients

Investigators combined microRNAs (miRNA) and mRNA expression profiles and bioinformatics analyses and then performed validation experiments. They identified 21 miRNAs and 2698 mRNAs that were differentially expressed in systemic sclerosis. [Sci Rep] Full Article

Extracellular Protonation Modulates Cell-Cell Interaction Mechanics and Tissue Invasion in Human Melanoma Cells

The authors tested the modulation of cell-cell-adhesion by extracellular pH and NHE1. MV3 tumor spheroids embedded in a collagen matrix unraveled the efficacy of cell-cell contact loosening and 3D emigration into an environment mimicking physiological confinement. [Sci Rep] Full Article

The Combined Action of Mast Cell Chymase, Tryptase and Carboxypeptidase A3 Protects against Melanoma Colonization of the Lung

Scientists assessed mice lacking either the chymase Mcpt4, the tryptase Mcpt6 or carboxypeptidase A3, as well as mice simultaneously lacking all three proteases, in a model of melanoma dissemination from blood to the lung. Although mice with individual deficiency in the respective proteases did not differ significantly from wildtype mice in the extent of melanoma colonization, mice with multiple protease deficiency exhibited a higher extent of melanoma colonization in lungs as compared to wildtype animals. [Oncotarget] Full Article

The TLR7 Agonist Imiquimod Induces Anti-Cancer Effects via Autophagic Cell Death and Enhances Anti-Tumoral and Systemic Immunity during Radiotherapy for Melanoma

Researchers evaluated the synergistic anti-cancer and anti-metastatic effects of the toll-like receptor (TLR)7 agonist imiquimod (IMQ) during radiotherapy for melanoma. The pretreatment of B16F10 or B16F1 cells with IMQ combined with γ-ionizing radiation led to enhanced cell death via autophagy, as demonstrated by increased expression levels of autophagy-related genes, and an increased number of autophagosomes in both cell lines. [Oncotarget] Full Article

The Impact of Melanoma Genetics on Treatment Response and Resistance in Clinical and Experimental Studies

The new sequencing, molecular, and bioinformatic technologies exploiting the melanoma genome for treatment decisions have significantly improved the understanding of melanoma pathogenesis, treatment response, and resistance for either targeted treatment or immune checkpoint blockade. [Cancer Metastasis Rev] Abstract

Targeting Invasive Properties of Melanoma Cells

The authors assess the major contributions towards understanding of the molecular biology of melanoma cell invasion with a focus on melanoma specific traits. These traits are based on the neural crest origin of melanoma cells and explain their intrinsic invasive nature. [FEBS J] Full Article

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

OncoSec to Present New Clinical Data from Phase II Combination Study

OncoSec Medical Incorporated will present new clinical data on ImmunoPulse^® IL-12, its lead program focused on oncology. [Press release from OncoSec Medical Incorporated discussing research to be presented at the 2017 American Association for Cancer Research & Society for Immunotherapy of Cancer (ASCO-SITC) Clinical Immuno-Oncology Symposium, Orlando] Press Release

Valeant Receives FDA Approval of SILIQ^™ (Brodalumab) for Moderate-to-Severe Plaque Psoriasis

Valeant Pharmaceuticals International, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved the Biologics License Application for SILIQ^™ injection, for subcutaneous use, a monoclonal antibody that targets the IL-17 receptor for patients with moderate-to-severe plaque psoriasis. [Valeant Pharmaceuticals International, Inc.] Press Release

Salk Scientist Awarded Inaugural SjöBerg Prize for Cancer Breakthrough

Salk Professor Tony Hunter, who holds an American Cancer Society Professorship, has been awarded $500,000 as part of the $1 million Royal Swedish Academy of Sciences’ inaugural Sjöberg Prize for Cancer Research for “groundbreaking studies of cellular processes that have led to the development of new and effective cancer drugs.” [Salk Institute for Biological Studies] Press Release

Delay in Hiring Science Advisers Intensifies Brexit Worries

Policy experts want scientists to be at the table when government decides on environmental protection and membership of international collaborations. [Nature News] Editorial

Why the CRISPR Patent Verdict Isn’t the End of the Story

The US Patent and Trademark Office issued a key verdict this week in the battle over the intellectual property rights to the potentially lucrative gene-editing technique CRISPR–Cas9. But the fight for patent rights to CRISPR technology is by no means over. [Nature News] Editorial

NEW Stem Cells and Regenerative Medicine 2^nd International Congress
April 19-21, 2017
Mashhad, Iran

NEW The Biology of Regenerative Medicine
April 25-27, 2017
Hinxton, United Kingdom

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

NEW Doctoral Student Position – Skin Biology (Karolinska Institutet)

NEW Postdoctoral Research Scientist – Melanoma (Ludwig Institute for Cancer Research)

NEW Postdoctoral Position – Translational Melanoma (University of Gothenburg)

Postdoctoral Associate – Cancer Biology (University of Florida)

Faculty Member – Melanoma (Oregon Health and Science University)

Postdoctoral Fellow – Cutaneous Lymphoma (City of Hope)

Bioinformatics Scientist – Cancer Biology (Genentech, Inc.)

Principal Scientist – Oncology (Janssen)

Tenure-Track Faculty Positions – Department of Biomedical Sciences (University of Pennsylvania)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Dermal Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.