Cancer Stem Cell News Volume 6.12 | Mar 29 2017

TOP STORY

A Distinct Role for Lgr5⁺ Stem Cells in Primary and Metastatic Colon Cancer

Investigators showed that the leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) identifies intestinal cancer stem cells in mouse tumors engineered to recapitulate the clinical progression of human colorectal cancer. They demonstrated that selective Lgr5⁺ cell ablation restricts primary tumor growth, but does not result in tumor regression. [Nature] Full Article | Editorial

(Ranked by impact factor of the journal)

Visualization and Targeting of LGR5⁺ Human Colon Cancer Stem Cells

The authors demonstrated that human LGR5⁺ colorectal cancer cells serve as cancer stem cells in growing cancer tissues. Lineage-tracing experiments with a CRISPR-Cas9-mediated LGR5–CreER knock-in allele revealed self-renewal and differentiation capacity of LGR5⁺ tumor cells. [Nature] Full Article

m⁶A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-Like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program

Researchers showed that the N⁶-methyladenosine (m⁶A) demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppressed the proliferation of patient-derived GSCs. Integrated transcriptome and m⁶A-seq analyses revealed altered expression of certain ALKBH5 target genes, including the transcription factor FOXM1. [Cancer Cell] Abstract | Graphical Abstract

Purine Synthesis Promotes Maintenance of Brain Tumor Initiating Cells in Glioma

Investigators link metabolic dysregulation in human brain tumor initiating cells (BTICs) to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility. [Nat Neurosci] Abstract

Self-Inflicted DNA Double-Strand Breaks Sustain Tumorigenicity and Stemness of Cancer Cells

The authors report a new class of self-inflicted DNA double-strand breaks (DSBs) that can drive tumor growth irrespective of their effects on genomic stability. They discovered a mechanism through which cancer cells cause DSBs in their own genome spontaneously independent of reactive oxygen species or replication stress. [Cell Res] Full Article

Identification of T Cell Target Antigens in Glioblastoma Stem-Like Cells Using an Integrated Proteomics-Based Approach in Patient Specimens

To identify T cell targets commonly presented by glioblastoma stem-like cells (GSCs) and their differentiated counterpart, scientists used a proteomics-based separation of GSC proteins in combination with a T cell activation assay. They identified novel immunogenic proteins, which frequently induced tumor-specific T cell responses in glioblastoma patients and were also detected in vitro in therapy-resistant quiescent, slow-cycling GSCs. [Acta Neuropathol] Abstract

Profiling Protein Expression in Circulating Tumor Cells Using Microfluidic Western Blotting

Protein profiling of circulating tumor cells (CTCs) would complement the recent advances in enumeration, transcriptomic and genomic characterization of these rare cells and help define their characteristics. The authors describe a microfluidic western blot for an eight-plex protein panel for individual CTCs derived from estrogen receptor-positive breast cancer patients. [Nat Commun] Full Article | Press Release

Skp2 Deficiency Restricts the Progression and Stem Cell Features of Castration-Resistant Prostate Cancer by Destabilizing Twist

Researchers discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of castration-resistant prostate cancer. In transgenic adenocarcinoma mouse prostate model, Skp2 depletion lead to a profound repression of prostate tumor growth and distal metastasis and substantially prolonged overall survival. [Oncogene] Full Article

Neuromedin U Alters Bioenergetics and Expands the Cancer Stem Cell Phenotype in HER2-Positive Breast Cancer

The authors found that ectopic over-expression of neuromedin U (NmU) in HER2-positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity. Overexpression of NmU also resulted in upregulation of epithelial-mesenchymal transition markers and increased IL-6 secretion which, together with aberrant metabolism, have all been associated with the cancer stem cell phenotype. [Int J Cancer] Abstract

TTF-1^– and/or CD56-Positive Circulating Tumor Cells in Patients with Small Cell Lung Cancer (SCLC)

Scientists evaluated the phenotypic circulating tumor cells (CTCs) heterogeneity (TTF-1⁺ and/or CD56⁺) in SCLC patients and correlated it with the CellSearch. One-chemotherapy cycle decreased both the number of positive patients and their CTC number, irrespectively of their phenotype and the detection method. [Sci Rep] Full Article

WT1 Expression in Breast Cancer Disrupts the Epithelial/Mesenchymal Balance of Tumor Cells and Correlates with the Metabolic Response to Docetaxel

Investigators provide a complete study of WT1 expression across different breast cancer subtypes as well as isoform specific expression analysis. Using in vitro cell lines, clinical samples and publicly available gene expression datasets, they demonstrated that WT1 plays a role in regulating the epithelial-mesenchymal balance of breast cancer cells and that WT1-expressing tumors are mainly associated with a mesenchymal phenotype. [Sci Rep] Full Article

The Challenge of Targeting Cancer Stem Cells to Halt Metastasis

The authors discuss the contribution of cancer stem cells (CSCs) to cancer metastasis and the scope of opportunities for therapeutic intervention. In particular, they consider CSC-targeting agents for which there is experimental evidence of anti-metastatic properties and which may have potential to eventually limit relapse and impede metastasis in patients. [Semin Cancer Biol] Full Article

Prostate Cancer Stem Cells and Nanotechnology: A Focus on Wnt Signaling

Scientists summarized the current understanding of prostate cancer stem cells and their self-renewal signaling pathways with a specific focus on Wnt signaling. [Front Pharmacol] Full Article

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Propanc Receives Patentability Opinion for Method of Treating Cancer Stem Cells

Propanc Health Group Corporation announced an International Search Report and Written Opinion was issued by the International Searching Authority on a Patent Cooperation Treaty (PCT) application recently submitted by the company. The PCT application covers a method for treating cancer stem cells by administering therapeutically effective amounts of trypsinogen and chymotrypsinogen. [Propanc Health Group Corporation] Press Release

ICR Scientists Awarded £1.5m Precision Medicine Funding for Targeted, Less Toxic Childhood Cancer Treatments

Scientists from the Institute of Cancer Research (ICR), London, have been awarded £1.5 million by the charity Children with Cancer UK to advance precision medicine in the UK and improve cancer treatment for children and young adults. [Institute of Cancer Research] Press Release

European Commission Considering Leap into Open-Access Publishing

One of Europe’s biggest science spenders could soon branch out into publishing. The European Commission, which spends more than €10 billion annually on research, may follow two other big league funders, the Wellcome Trust and the Bill & Melinda Gates Foundation, and set up a “publishing platform” for the scientists it funds, in an attempt to accelerate the transition to open-access publishing in Europe. [ScienceInsider] Editorial

Europe Says University of California Deserves Broad Patent for CRISPR

The European Patent Office announced its “intention to grant a patent” to the University of California (UC) for its broad-based claims about the genome-editing tool popularly known as CRISPR. UC, on behalf of several parties, has been in a pitched battle with the Broad Institute of Cambridge, Massachusetts, over CRISPR patents, and the new decision marks a sharp departure from the position of the U.S. Patent and Trademark Office. [ScienceInsider] Editorial

Playing No Trump at AAAS Policy Forum

The relationship between U.S. scientists and the Trump administration hit a new low after organizers of a major annual science policy conference were unable to find anyone willing to discuss the president’s priorities. [ScienceInsider] Editorial

NEW Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging
May 21-26, 2017
West Palm Beach, United States

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NEW Postdoctoral Fellow – Breast Cancer Stem Cell (University of Kentucky)

Postdoctoral Position – Stem Cell Research (Helmholtz Association)

Postdoctoral Training Fellow – Stem Cell Dynamics in the Adult Hippocampus (The Francis Crick Institute)

Postdoctoral Fellow – Cancer Research (Houston Methodist Research Institute)

Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine)

Postdoctoral Position – Cancer/Normal Stem Cells (Johns Hopkins University)

Postdoctoral Research Fellow Positions – Biomedical Research (Cincinnati Children’s Hospital Medical Center)

Principal Investigator – Cancer Research and Oncology Drug Discovery (Southern Research Institute)

Postdoctoral Fellow – Cancer Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cell Cycle Control and Tumorigenesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Ubiquitin System and Cancer (Fred Hutchinson Cancer Research Center)

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