Cancer Stem Cell News Volume 5.41 | Oct 19 2016

TOP STORY

Snail1-Dependent p53 Repression Regulates Expansion and Activity of Tumor-Initiating Cells in Breast Cancer

Using a Snail1 conditional knockout model of mouse breast cancer that maintains wild-type p53, researchers found that Snail1 plays an essential role in tumor progression by controlling the expansion and activity of tumor-initiating cells in preneoplastic glands and established tumors, whereas it is not required for normal mammary development. [Nat Cell Biol] Abstract

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Long-Term Exposure to Bisphenol A or Benzo(a)Pyrene Alters the Fate of Human Mammary Epithelial Stem Cells in Response to BMP2 and BMP4, by Pre-Activating BMP Signaling

Scientists demonstrated that chronic exposure to low doses of bisphenol A or benzo(a)pyrene alone has little effect on stem cells (SCs) properties of MCF10A cells. Conversely, they showed that this exposure affects the response of immature epithelial cells to bone morphogenetic protein (BMP) 2 and BMP4. [Cell Death Differ] Full Article

Tetraspanin CD9 Stabilizes gp130 by Preventing Its Ubiquitin-Dependent Lysosomal Degradation to Promote STAT3 Activation in Glioma Stem Cells

The authors report that CD9 stabilizes the IL-6 receptor glycoprotein 130 (gp130) by preventing its ubiquitin-dependent lysosomal degradation to facilitate the STAT3 activation in glioma stem cells (GSCs). CD9 is preferentially expressed in GSCs of human glioblastoma tumors. [Cell Death Differ] Abstract

CDK4 Regulates Cancer Stemness and Is a Novel Therapeutic Target for Triple-Negative Breast Cancer

Researchers found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. They found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients. [Sci Rep] Full Article

The ETS Factor ESE3/EHF Represses IL-6 Preventing STAT3 Activation and Expansion of the Prostate Cancer Stem-Like Compartment

Researchers identified IL-6 as a direct target of ESE3/EHF that is activated in prostate epithelial cells upon loss of ESE3/EHF. ESE3/EHF and IL-6 were significantly inversely correlated in prostate tumors. [Oncotarget] Full Article

Targeting Aberrant Expression of Notch-1 in ALDH⁺ Cancer Stem Cells in Breast Cancer

Scientists examined the functional and clinical significance of aldehyde dehydrogenase (ALDH) expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues versus normal breast tissues. [Mol Carcinog] Abstract

Doxycycline Inhibits the Cancer Stem Cell Phenotype and Epithelial-to-Mesenchymal Transition in Breast Cancer

The authors investigated the mechanism by which doxycycline exerts its inhibitory effects on the properties of breast cancer cells and breast cancer stem cells (BCSCs), such as mammosphere forming efficiency, invasion, migration, apoptosis, the expression of stem cell markers and epithelial-to-mesenchymal transition related markers of breast cancer cells. [Cell Cycle] Abstract

Proteomic Analysis of Pancreatic Cancer Stem Cells: Functional Role of Fatty Acid Synthesis and Mevalonate Pathways

To identify the modulated proteins of pancreatic cancer stem cells (CSCs), iTRAQ-based proteomic analysis was performed to compare the proteome of Panc1 CSCs and Panc1 parental cells, identifying 230 modulated proteins. Pathway analysis revealed activation of glycolysis, the pentose phosphate pathway, the pyruvate-malate cycle, and lipid metabolism as well as downregulation of the Krebs cycle, the splicesome and non-homologous end joining. [J Proteomics] Abstract

STAT3 as a Potential Therapeutic Target in ALDH⁺ and CD44⁺/CD24⁺ Stem Cell-Like Pancreatic Cancer Cells

Whether STAT3 is activated in stem cell-like pancreatic cancer cells and the effect of STAT3 inhibition, is still unknown. Flow cytometry was used to isolate pancreatic cancer stem-like cells which are identified by both aldehyde dehydrogenase-positive (ALDH⁺) as well as cluster of differentiation (CD) 44-positive/CD24-positive subpopulations. [Int J Oncol] Abstract

Heterogeneity of Cancer Stem Cells: Rationale for Targeting the Stem Cell Niche

The authors portray potentially clinically-relevant hallmarks of cancer stem cells and focus on their recently appreciated properties of cell variability and plasticity, both of which make them elusive targets for cancer therapies. They reason that this ‘disguise in heterogeneity’ has fundamental implications for clinical management and elaborate on rational strategies to combat this diversity and target a broad range of tumorigenic cells. [Biochim Biophys Acta] Abstract

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GenomeDx’s Decipher GRID Aids in Development and Validation of the First Molecular Signature to Predict Response to Radiotherapy in Prostate Cancer

GenomeDx Biosciences announced that gene expression profiles in the company’s Decipher Genomics Resource Information Database (Decipher GRID^®) were used in the discovery of Post-Operative Radiation Therapy Outcomes Score, the first validated molecular signature developed to predict patients’ response to radiotherapy in prostate cancer. [GenomeDx Biosciences] Press Release

First Patient in Malaysia Receives TheraSphere^™ Radioembolization Therapy

BTG plc announced that the first patient in Malaysia was treated with TheraSphere^™ – a transarterial radioembolization therapy, which targets primary liver cancer and metastatic colorectal cancer with a powerful dose of radiation while minimizing exposure to healthy tissue. [BTG plc] Press Release

PharmaEngine Announces Initiation of Phase Ib/II Trial of PEP503 (NBTXR3) in Head and Neck Cancer

PharmaEngine Inc. announced that the first patient has been dosed in a Phase Ib/II trial of PEP503 of head and neck squamous cell carcinoma at Keelung Chang Gung Memorial Hospital in Keelung, Taiwan. [PharmaEngine Inc. (PR Newswire Association LLC.)] Press Release

Atrin Pharmaceuticals Awarded $300,000 Phase I Contract for Development of Highly Specific ATR inhibitors for Targeted Cancer Treatment

Atrin Pharmaceuticals, Inc. announced receipt of a Phase I Small Business Technology Transfer Award for approximately $300,000 from the National Cancer Institute of the National Institutes of Health. The award supports Atrin’s development of highly specific inhibitors of ATR for the targeted treatment of a broad spectrum of cancers. [Atrin Pharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release

Budget Cap Would Stifle Brazilian Science, Critics Say

Brazil’s economy is in free fall, and the new government has a controversial remedy: a constitutional amendment that would cap public spending for the next 20 years. The proposal, known as PEC 241, would prohibit all three branches of Brazil’s government to raise yearly expenditures above the inflation rate, essentially freezing spending at current levels for 2 decades. [Science Insider] Editorial

Biden’s Moonshot Cancer Plan Calls for More Data Sharing

Vice President Joe Biden released his vision for doubling progress against cancer over 5 years. It includes numerous policy recommendations and a laundry list of projects by the National Cancer Institute and other federal agencies that would require additional funding. [Science Insider] Editorial

U.S. and Cuban Biomedical Researchers Are Free to Collaborate

The U.S. Department of the Treasury has authorized U.S. scientists to freely collaborate with Cuban counterparts on everything from cancer therapies to combating the Zika virus. [Science Insider] Editorial

NEW Molecular and Cellular Basis of Breast Cancer Risk and Prevention
November 12, 2016
Tampa, United States

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NEW Lecturer – Cancer Biology (NUI Galway)

NEW Associate Professor – Experimental Radiation Oncology (The University of Texas MD Anderson Cancer Center)

Research Associate – Plasticity and Cancer (University of Cambridge)

Assistant Professor (Tenure Track) – Mechanisms Related to Aging, Cancer and Stem Cell Biology (The Hong Kong University of Science and Technology)

Scientific Developer – Computational Systems Biology of Cancer (Institut Curie)

Post-Doctoral Researcher – Influential Nodes and Links in Multi-Level Cancer-Related Networks (Luxembourg Institute of Health)

Two Assistant Professor Positions – Molecular Medicine (University of Georgia)

Postdoctoral Associate – Glioma Stem Cell Biology and Cerebral Organoid (Weill Cornell Medicine)

Postdoctoral Positions – Stem Cell Research, Hematopoiesis, Cancer, Genome Editing (Icahn School of Medicine at Mount Sinai)

Postdoctoral Position – Tumor Immunology (Memorial Sloan Kettering Cancer Center)

Postdoctoral Fellow – Laboratory Studies Brain Cancer Stem Cells (Houston Methodist)

Associate Scientist – Epigenetics of Cancer (Celgene Corporation)

Postdoctoral Position – Metastatic Breast Cancer (Purdue Center for Cancer Research)

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