Dermal Cell News Volume 3.03 | Jan 30 2017

TOP STORY

Rhomboid Family Member 2 Regulates Cytoskeletal Stress-Associated Keratin 16

Investigators showed that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with keratin 16 (K16). K16 expression was absent in the thinned footpads of irhom2^−/− mice compared with irhom2^+/+ mice, due to reduced keratinocyte proliferation. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Similarities and Differences in the Transcriptional Control of Expression of the Mouse TSLP Gene in Skin Epidermis and Intestinal Epithelium

Researchers demonstrated that in epidermal keratinocytes, unliganded heterodimers of vitamin D receptor/retinoid X receptor (RXR)-α and retinoic acid receptor-γ/RXR-β are bound as repressing complexes to their cognate DNA-binding sequence(s) in the thymic stromal lymphopoietin (TSLP) promoter regulatory region. [Proc Natl Acad Sci USA] Abstract

SKIN CANCERS & DISORDERS

PDE4D Promotes FAK-Mediated Cell Invasion in BRAF-Mutated Melanoma

The authors showed that phosphodiesterase type 4 (PDE4) D is overexpressed in BRAF-mutated melanoma cell lines, constitutively disrupting the cyclic AMP pathway activation. PDE4D promoted melanoma invasion by interacting with focal adhesion kinase (FAK) through the scaffolding protein RACK1. [Oncogene] Abstract

Oncogenic BRAF Fusions in Mucosal Melanomas Activate the MAPK Pathway and Are Sensitive to MEK/PI3K Inhibition or MEK/CDK4/6 Inhibition

Forty-six primary mucosal melanomas underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted. Scientists tested the in vitro and in vivo efficacy of vemurafenib, trametinib, BKM120 or LEE011 alone and in combination. Trametinib effectively inhibited tumor cell growth in vitro, but the combination of trametinib and BKM120 or LEE011 yielded more than additive anti-tumor effects both in vitro and in vivo in a melanoma cells harboring the BRAF fusion. [Oncogene] Abstract

Highly Potent Non-Carboxylic Acid Autotaxin Inhibitors Reduce Melanoma Metastasis and Chemotherapeutic Resistance of Breast Cancer Stem Cells

Researchers report on inhibitors of autotaxin (ATX) derived by lead optimization of the benzene-sulfonamide in silico hit compound 3. The new analogues provided a comprehensive SAR of the benzene-sulfonamide scaffold that yielded a series of highly potent ATX inhibitors. In particular, compound 3b potently reduced in vitro chemotherapeutic resistance of 4T1 breast cancer stem-like cells to paclitaxel and reduced significantly B16 melanoma metastasis in vivo. [J Med Chem] Abstract

The Role of the Cancer Stem Cell Marker CD271 in DNA Damage Response and Drug Resistance of Melanoma Cells

Investigators observed high cell surface and total levels of nerve growth factor receptor/CD271, a marker of melanoma-initiating cells, in sub-populations of chemoresistant cell lines. CD271 expression was increased in drug-sensitive cells but not resistant cells in response to DNA-damaging chemotherapeutics etoposide, fotemustine and cisplatin. [Oncogenesis] Full Article

Ladarixin, a Dual CXCR1/2 Inhibitor, Attenuates Experimental Melanomas Harboring Different Molecular Defects by Affecting Malignant Cells and Tumor Microenvironment

Scientists investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas. The data showed that LDX-mediated inhibition of CXCR1/2 abrogated motility and induced apoptosis in cultured cutaneous and uveal melanoma cells and xenografts independently of the molecular defects associated with the malignant phenotype. [Oncotarget] Full Article

HERV-K Activation Is Strictly Required to Sustain CD133⁺ Melanoma Cells with Stemness Features

Researchers investigated the correlation between human endogenous retrovirus type K (HERV-K) and the CD133 positive (CD133⁺) melanoma cells during microenvironmental modifications. Melanoma cells, exposed to stem cell media, underwent phenotype-switching and expansion of CD133⁺ melanoma cells, concomitantly promoted by HERV-K activation. [J Exp Clin Cancer Res] Full Article

IgG1-iS18 Impedes the Adhesive and Invasive Potential of Early and Late Stage Malignant Melanoma Cells

The authors investigated the role of 37 kDa/67 kDa laminin receptor (LRP/LR) on the metastatic potential of early and late stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. [Exp Cell Res] Abstract

Ultraviolet Radiation Induced Down-Regulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma

Investigators have shown that nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) is expressed in human basal cell carcinomas. They demonstrated that ultraviolet B exposure blocks Ca²⁺ mobilization by downregulating the expression of sarco/endoplasmic reticulum Ca²⁺ -ATPase (SERCA2), a component of store-operated Ca²⁺ entry that leads to activation of the NLRP3 inflammasome. [Photochem Photobiol] Abstract

Stromal Microenvironment in Type VII Collagen-Deficient Skin: The Ground for Squamous Cell Carcinoma Development

Researchers discuss recent knowledge on microenvironment alterations in recessive dystrophic epidermolysis bullosa, highlighting possible therapeutic targets to prevent and/or delay fibrosis and squamous cell carcinoma development. [Matrix Biol] Abstract

BRAF Inhibitor-Associated Cutaneous Squamous Cell Carcinoma: New Mechanistic Insight, Emerging Evidence for a Viral Involvement, and Perspectives on Clinical Management

The authors summarize the clinical and molecular profile of BRAF inhibitor-associated cutaneous squamous cell carcinomas, with a focus on factors that may contribute to disease pathogenesis. In particular, they discuss the emerging evidence pointing toward viral involvement in BRAF inhibitor-induced cutaneous neoplasms and offer new perspectives on future therapeutic interventions. [Br J Dermatol] Abstract

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

The Immunotherapy, Pembrolizumab, Is Active against Mucosal Melanoma Tumors

Clinical trials of a new immunotherapy, pembrolizumab, have shown that it prolongs life significantly for patients with bladder cancer and is active against a rare sub-type of melanoma, called mucosal melanoma. [Press release from Princess Margaret Cancer Centre (EurekAlert!) discussing research presented at the European Cancer Congress 2017, Amsterdam] Press Release

American Skin Association Announces 2017 Research Scholar Awards and Research Grants

As American Skin Association celebrates 30 years of promoting good skin health through research and education, they continue their long history of awarding significant grants by announcing the funding of 18 critical research grants for 2017. Funding has been awarded in a variety of concentrations, including melanoma, non-melanoma skin cancer, psoriasis and inflammatory diseases, vitiligo and pigment cell disorders, and childhood skin diseases. [American Skin Association (PR Newswire Association LLC.)] Press Release

CHORI Scientist and Abate Med Founder Collaborating to Find a Lasting Treatment for Atopic Dermatitis

Laura Hertel, PhD, a virologist at Children’s Hospital Oakland Research Institute (CHORI), has received a $100,000 grant from Abate Med’s founder, Dr. David Paslin, for a pre-clinical study on the efficacy of using a protein made by a common virus that infects the skin, to treat the cutaneous manifestations of atopic dermatitis. [Children’s Hospital Oakland Research Institute (Newswise, Inc)] Press Release

Proposed U.S. Biotech Rules Raise Industry Hopes and Anxieties

Makers of genetically engineered products have long been on the lookout for changes in U.S. regulations. The system that divvies up the safety review of these products between the Food and Drug Administration, Environmental Protection Agency, and U.S. Department of Agriculture is in the middle of a years-long overhaul, in part to accommodate modern gene-editing technologies such as CRISPR. And a set of new proposals released last week offers hints about what those agencies still hope to change. [ScienceInsider] Editorial

Trump Agenda Threatens US Legacy of Science Diplomacy

A newly minted leader with no experience governing at home or establishing policy abroad now oversees the United States’ vast diplomatic enterprise. US President Donald Trump has a deep bench of scientific and technical expertise to tap across multiple government agencies — but it is not clear that he will use it. [Nature News] Editorial

NEW AACR Annual Meeting 2017
April 1-5, 2017
Washington, D.C., United States

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

NEW Postdoctoral Associate – Cancer Biology (University of Florida)

PhD Studentships – Skin and Joint Inflammation (Cardiff University)

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)

Two PhD Positions – Functional Polymer Composites for Skin Applications (Technical University of Denmark)

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

Postdoctoral Research Fellow – Melanoma (Dana-Farber Cancer Institute)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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