Dermal Cell News Volume 3.02 | Jan 23 2017

TOP STORY

Keeping Skin Cancer in Check

Researchers analyzed human tissue samples of skin cancer patients. They collected samples of different stages of melanomas and analyzed how the expression of Par3 and P-cadherin correlated with tumor growth. They found that with further progression of the tumor, the expression of Par3 decreased, while the contacts between tumor cells and the neighboring epithelium showed P-cadherin accumulation. [Press release from the University of Cologne discussing online prepublication in J Exp Med] Press Release | Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

IGF1R Signaling Acts on the Anagen to Catagen Transition in the Hair Cycle

The authors studied a conditional and inducible knockout of the IGF1 receptor (IGF1R) in keratin 15-expressing bulge cells. Deletion of IGF1R after the development of the skin appendages in K15-IGF1R^KO mice showed no abnormalities in epidermal homeostasis. [Exp Dermatol] Abstract

SKIN CANCERS & DISORDERS

SDHD Promoter Mutations Ablate GABP Transcription Factor Binding in Melanoma

Researchers found that expression of SDHD in melanoma correlated with the expression of multiple ETS-transcription factors, particularly in SDHD promoter wild-type samples. Using siRNA-mediated knockdown across multiple melanoma cell lines, they determined that loss of GABPA resulted in reduced SDHD expression at both RNA and protein levels. [Cancer Res] Abstract

WNT/β-Catenin Signaling Regulates Mitochondrial Activity to Alter the Oncogenic Potential of Melanoma in a PTEN-Dependent Manner

Investigators found that expression of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alters the invasive potential of melanoma cells in response to WNT/β-catenin signaling, correlating with differing metabolic profiles. This altered the bioenergetic potential and mitochondrial activity of melanoma cells, triggered through regulation of pro-survival autophagy. [Oncogene] Full Article

Unbalancing p53/Mdm2/IGF-1R Axis by Mdm2 Activation Restrains the IGF-1-Dependent Invasive Phenotype of Skin Melanoma

The authors investigated the effects of pharmacological mouse double-minute 2 homolog (Mdm2) release from the Mdm2/p53 complex on the expression and function of the insulin-like growth factor type 1 receptor (IGF-1R). Nutlin-3 treatment increased IGF-1R/Mdm2 association with enhanced IGF-1R ubiquitination and a dual functional outcome: receptor downregulation and selective downstream signaling activation confined to the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. [Oncogene] Full Article

Cutaneous HPV8 and MmuPV1 E6 Proteins Target the NOTCH and TGF-β Tumor Suppressors to Inhibit Differentiation and Sustain Keratinocyte Proliferation

To determine whether MmuPV1 may be an appropriate model to mechanistically dissect the molecular contributions of cutaneous human papillomavirus (HPV) infections to skin carcinogenesis, researchers investigated whether MmuPV1 E6 shares biological and biochemical activities with HPV8 E6. They report that the HPV8 and MmuPV1 E6 proteins share the ability to bind to the MAML1 and SMAD2/SMAD3 transcriptional cofactors of NOTCH and TGF-beta signaling, respectively. [PLoS Pathog] Full Article

FAK Regulates E-Cadherin Expression via p-Src^Y416/p-ERK_1/2/p-Stat3^Y705 and PPARγ/miR-125b/Stat3 Signaling Pathway in B16F10 Melanoma Cells

Scientists present a signaling pathway involved in the regulation of melanoma cell migration by focal adhesion kinase (FAK). They found that the interference of FAK expression suppressed B16F10 cell migration/metastasis, and altered the expressions of genes involved in melanoma migration/metastasis. [Oncotarget] Full Article

The Nitrobenzoxadiazole Derivative MC3181 Blocks Melanoma Invasion and Metastasis

The novel nitrobenzoxadiazole derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Researchers report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. [Oncotarget] Full Article

Melanoma Cell Adhesion and Migration Is Modulated by the Uronyl 2-O Sulfotransferase

To demonstrate an impact of 2-O sulfation in metastasis investigators knocked-down uronyl-2-O sulfotransferase (Ust) in mouse melanoma cells. This significantly reduced the amount of Ust protein and enzyme activity. In vitro cell motility and adhesion were significantly reduced correlating with the decrease of cellular Ust protein. [PLoS One] Full Article

Divergence of cAMP Signaling Pathways Mediating Augmented Nucleotide Excision Repair and Pigment Induction in Melanocytes

Researchers investigated the interdependence of cAMP-mediated melanin upregulation and cAMP-enhanced DNA repair in primary human melanocytes and a melanoma cell line. They observed that the ataxia telangiectasia mutated and Rad3 related-dependent molecular pathway linking cAMP signaling to the nucleotide excision repair pathway is independent of MITF activation. [Exp Dermatol] Abstract

KRAS, NRAS and BRAF Mutations in Colorectal Cancer and Melanoma

The authors focus on the genes, which are frequently mutated in various cancers and are known to be important in the advance and progression of colorectal cancer and melanoma, namely KRAS, NRAS and BRAF. [Med Oncol] Abstract

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

Infinity Presents Preclinical Data and Phase I Clinical Data on IPI-549 at PI3K Keystone Symposia Conference

Infinity Pharmaceuticals, Inc. presented preclinical data for IPI-549, an oral immuno-oncology development candidate that selectively inhibits phosphoinositide-3-kinase (PI3K)-gamma. Preclinical data showed that IPI-549 is able to help overcome resistance to checkpoint inhibition by remodeling the immune-suppressive tumor microenvironment primarily through its effects on myeloid cells, a type of cell considered to be involved in suppressing immune response against tumors. [Press release from Infinity Pharmaceuticals, Inc. discussing research presented at the 2017 Keystone Symposia Conference – PI3K Pathways in Immunology, Growth Disorders and Cancer, Santa Fe] Press Release

The German National Center for Tumor Diseases (NCT) Heidelberg and Protagen AG Investigate Responsiveness to Checkpoint Inhibitors in Melanoma

The German National Center for Tumor Diseases Heidelberg and Protagen AG announced a collaboration to utilize Protagen’s SeroTag^® technology to identify biomarkers that predict therapy responsiveness and the detection of immune-related adverse events in melanoma patients treated with checkpoint inhibitors. [Protagen AG] Press Release

Statement From FDA Commissioner Robert Califf, M.D. Announcing FDA Oncology Center of Excellence Launch

The U.S. Food and Drug Administration (FDA) established the Oncology Center of Excellence and appointed Dr. Richard Pazdur as its director. This will make oncology the first disease area to have a coordinated clinical review of drugs, biologics and devices across the agency’s three medical product centers. [U.S. Food and Drug Administration] Press Release

Scientists Join Massive Protest against Trump

The women in white lab coats didn’t expect to be treated like celebrities. The group of scientists, dozens strong, came to Washington DC to join the Women’s March, a massive protest against the brand-new US President, Donald Trump. But as they navigated the dense crowd near the National Air and Space Museum, the researchers were greeted by shouts of “We love science!” Eager strangers asked the scientists to pose for photographs with the signs they carried, which bore slogans such as “Stand up 4 Science” and “Science does not discriminate.” [Nature News] Editorial

Wanted: A Leader for the Toughest Job in Global Health

Global health watchers will pay close attention to Geneva, Switzerland when the World Health Organization (WHO) will announce the final three candidates to take the agency’s top job. The decision by WHO’s Executive Board, made up of representatives of 34 member states, follows months of behind-the-scenes jockeying, campaigning by the candidates, and intense speculation. It will be followed in May by a final vote by WHO’s 194 member states. [ScienceInsider] Editorial

Biotech Firm Backs Controversial CRISPR Challenger

A major enzyme manufacturer has signed an agreement with a Chinese university to explore uses for a protein claimed to be a powerful alternative to the popular genome-editing tool CRISPR–Cas9. Several scientists have failed to reproduce the results of the paper that first made the claim and doubt that the protein, NgAgo, works as a gene editor. [Nature News] Editorial

NEW ESMO Symposium on Signaling Pathways in Cancer 2017
March 17-18, 2017
Barcelona, Spain

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

NEW PhD Studentships – Skin and Joint Inflammation (Cardiff University)

NEW Faculty Member – Melanoma (Oregon Health and Science University)

NEW Postdoctoral Fellow – Cutaneous Lymphoma (City of Hope)

NEW Bioinformatics Scientist – Cancer Biology (Genentech, Inc.)

NEW Principal Scientist – Oncology (Janssen)

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

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

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)

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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