Dermal Cell News Volume 3.01 | Jan 16 2017

TOP STORY

Adaptive Resistance of Melanoma Cells to RAF Inhibition via Reversible Induction of a Slowly Dividing De‐Differentiated State

Treatment of BRAF-mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. Researchers used live-cell imaging, single-cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. [Mol Syst Biol] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Clasp2 Ensures Mitotic Fidelity and Prevents Differentiation of Epidermal Keratinocytes

Using cultured primary keratinocytes, scientists reported that the expression of the mammalian microtubule and kinetochore-associated protein Clasp2 is intimately associated to the basal proliferative makeup of keratinocytes, and its deficiency leads to premature differentiation. [J Cell Sci] Abstract | Full Article

Hypoxia Regulates mTORC1-Mediated Keratinocyte Motility and Migration via the AMPK Pathway

Although the authors have previously found that hypoxia induces keratinocyte migration, the underlying mechanism remains unknown. Here, they observed that hypoxia increased mTORC1 activity. Using cell migration assay and a Zeiss chamber equipped with imaging system, they also demonstrated that mTORC1 downregulation reversed hypoxia-induced keratinocyte motility and lateral migration. [PLoS One] Full Article

SKIN CANCERS & DISORDERS

KLF4 Is Regulated by RAS/RAF/MEK/ERK Signaling through E2F1 and Promotes Melanoma Cell Growth

The Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that plays a critical role in embryonic development, stemness and cancer, where it can act either as oncogene or tumor suppressor. Scientists addressed the function of KLF4 in melanoma and its interaction with the mitogen activated protein kinase signaling pathway. They found that KLF4 was highly expressed in a subset of human melanomas. [Oncogene] Full Article

SOCS1 Favors the Epithelial-Mesenchymal Transition in Melanoma, Promotes Tumor Progression and Prevents Antitumor Immunity by PD-L1 Expression

The authors aimed to analyze the SOCS1 cell signaling and expression of proteins relevant to tumor development. They showed the role of SOCS1 in murine melanoma development and the potential of SOCS1-silenced tumor cells in raising an effective anti-melanoma immune response. [Sci Rep] Full Article

Antiproliferative Effects of 1α-OH-vitD₃ in Malignant Melanoma: Potential Therapeutic Implications

The biological effects of 1α-hydroxycholecalciferol on experimental melanoma models were investigated. Treatment with 1α-hydroxycholecalciferol induced antiproliferative effects on melanoma cells in vitro and in vivo, modulating the expression of cell cycle key regulatory molecules. [Sci Rep] Full Article

Vemurafenib and Trametinib Reduce Expression of CTGF and IL-8 in ^V600EBRAF Melanoma Cells

Investigators explored the response of ^V600EBRAF melanoma cells derived from surgical specimens and grown in stem cell medium to vemurafenib and trametinib, drugs targeting the activity of ^V600EBRAF and MEK1/2, respectively. [Lab Invest] Abstract

Application of Aluminum Chloride Phthalocyanine-Loaded Solid Lipid Nanoparticles for Photodynamic Inactivation of Melanoma Cells

Aluminum chloride phthalocyanine (ClAlPc) is used as a photosensitizer in photodynamic therapy; however, its high hydrophobicity hampers its photodynamic activity under physiological conditions. The aim of this study was to produce solid lipid nanoparticles (SLN) containing ClAlPc using the direct emulsification method. Compared to free ClAlPc, ClAlPc/SLN exerted outstanding phototoxicity effects in vitro against melanoma cells. [Int J Pharm] Abstract

Anticancer Properties of Ester Derivatives of Betulin in Human Metastatic Melanoma Cells (Me-45)

Researchers examined the anticancer properties of the ester derivatives of betulin compared to their precursors in a malignant melanoma cell line. They assessed five amino acid esters of betulin. The highest biological activity was observed with the lysine ester. The betulin ester derivatives showed enhanced antitumor activity compared to their non-modified precursors. [Cancer Cell Int] Full Article

Peroxisome Proliferator-Activated Receptor α (PPARα) Contributes to Control of Melanogenesis in B16 F10 Melanoma Cells

Investigators aimed to check how the PPARα expression level affects the antimelanogenic activity of fenofibrate and whether PPARα modulates melanogenesis independently of its agonist. They observed that cells overexpressing PPARα were almost amelanotic and cells with reduced PPARα protein level were heavily melanized. They concluded that fenofibrate works as a strong depigmenting agent, which acts independently of PPARα, but in an additive fashion. [Arch Dermatol Res] Abstract

Melanoma in Congenital Melanocytic Nevi

Congenital melanocytic nevi are a known risk factor for melanoma, with the greatest risk currently thought to be in childhood. The authors review the world literature and their center’s experience over the last 25 years, including the molecular characteristics of melanoma in these patients and new melanoma incidence and outcome data from their prospective cohort. [Br J Dermatol] Abstract

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Valeant Pharmaceuticals Announces Results of Second Phase III Study for Psoriasis Treatment IDP-118

Valeant Pharmaceuticals International, Inc. announced positive results from a second confirmatory pivotal Phase III, multicenter double-blind, randomized, vehicle-controlled clinical study to assess the safety and efficacy of IDP-118 lotion in the treatment of plaque psoriasis. [Valeant Pharmaceuticals International, Inc.] Press Release

MD Anderson and Deerfield Management Create Vescor LLC to Develop Novel Therapeutics Based on Inhibiting Autophagy for Treatment of Specific Cancers

Vescor LLC has been formed by The University of Texas MD Anderson Cancer Center, Deerfield Management and two leading autophagy experts, Eileen White, Ph.D., deputy director and associate director for Basic Science, Rutgers Cancer Institute of New Jersey, and Alec Kimmelman, M.D., Ph.D., chairman, Department of Radiation Oncology at NYU Langone Medical Center and a member of the Perlmutter Cancer Center at NYU Langone. [The University of Texas MD Anderson Cancer Center] Press Release

Surprising Contenders Emerge for Trump’s NIH Chief

Could US president-elect Donald Trump be close to choosing a leader for the National Institutes of Health (NIH)? Current NIH chief Francis Collins and Representative Andy Harris (Republican, Maryland), both front-runners for job, met separately with Trump, as did billionaire surgeon Patrick Soon-Shiong. Several people familiar with the Collins and Harris meetings described them as job interviews. [Nature Breaking News] Editorial

Gates Foundation Research Can’t Be Published in Top Journals

One of the world’s most influential global health charities says that the research it funds cannot currently be published in several leading journals, because the journals do not comply with its open-access policy. [Nature News] Editorial

NEW Stem Cells in Drug Discovery
March 6-7, 2017
Cambridge, United Kingdom

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

Senior Research Fellow/Associate Research Professor – Allergic Inflammation and Skin Cancer (University of South Australia)

Tenure-Track Faculty Positions – Melanoma Cancer Research (Case Western Reserve University)

Postdoctoral Fellow – Cancer Biology (European Molecular Biology Laboratory)

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

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

Assistant/Associate Professor – Melanoma (Case Western Reserve University)

Assistant Professor – Cancer Research (National University of Singapore)

Postdoctoral Fellow – Cancer Research (National University of Singapore)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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