Cancer Stem Cell News Volume 6.11 | Mar 22 2017

TOP STORY

Scientists Find Possible Achilles Heel of Treatment Resistant Cancers

Scientists identified two signaling proteins in cancer cells that make them resistant to chemotherapy, and showed that blocking the proteins along with chemotherapy eliminated human leukemia in mouse models. [Press release from the Cincinnati Children’s Hospital Medical Center discussing online prepublication in Nature Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Inhibition of Pol I Transcription Treats Murine and Human AML by Targeting the Leukemia-Initiating Cell Population

Investigators revealed that the selective inhibitor of RNA polymerase I (Pol I) transcription, CX-5461, effectively treats aggressive acute myeloid leukemia (AML), including MLL-driven AML, and outperforms standard chemotherapies. In addition to the previously characterized mechanism of action of CX-5461, the induction of p53-dependant apoptotic cell death, inhibition of Pol I transcription also demonstrated potent efficacy in p53null AML in vivo. [Blood] Abstract

Pre‐Clinical Validation of a Selective Anti‐Cancer Stem Cell Therapy for Numb‐Deficient Human Breast Cancers

Using patient‐derived xenografts, researchers showed that expansion of the cancer stem cell (CSC) pool, due to altered self‐renewing divisions, is also a feature of Numb‐deficient human breast cancers. In these cancers, using the inhibitor Nutlin‐3 to restore p53, they corrected the defective self‐renewal properties of Numb‐deficient CSCs and inhibited CSC expansion, with a marked effect on tumorigenicity and metastasis. [EMBO Mol Med] Full Article | Graphical Abstract

m⁶A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells

The authors showed that m⁶A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promoted human GSC growth, self-renewal, and tumorigenesis. [Cell Rep] Full Article | Graphical Abstract

Time- and Cell-Resolved Dynamics of Redox-Sensitive Nrf2, HIF and NF-κB Activities in 3D Spheroids Enriched for Cancer Stem Cells

Cancer cells have an altered redox status, with changes in intracellular signaling pathways. Investigators stably transfected HCT116 cells with a pTRAF reporter that enabled time- and cell-resolved activity monitoring of three redox-regulated transcription factors Nrf2, HIF and NF-κB in spheroids enriched for cancer stem cells. [Redox Biol] Full Article | Graphical Abstract

A 3D Model of Tumor Angiogenic Microenvironment to Monitor Hypoxia Effects on Cell Interactions and Cancer Stem Cell Selection

Scientists describe a 3D model of melanoma growth in its environment. Introducing means to mimic tumor angiogenesis, which turns on tumor progression, the model showed that melanoma tumor spheroids allow reconstitution of solid tumors with stromal cells. Hypoxia was the key parameter that selected and stabilized melanoma cancer stem like cells phenotype based on aldehyde dehydrogenase expression as the best criterion. The 3D-tumor-model demonstrated the distinct reactivity of endothelial cells toward tumor cells in terms of cellular cross-talk and humoral response. [Cancer Lett] Full Article

A CD44v⁺ Subpopulation of Breast Cancer Stem-Like Cells with Enhanced Lung Metastasis Capacity

Researchers showed that among the CD24⁻/CD44⁺ breast cancer stem-like cells, a subset expressing the variant isoform of CD44 (CD44v) displays significantly higher capacity of lung metastasis than that expressing the standard CD44 isoform, CD44s. Increasing or reducing the CD44v/CD44s ratio of breast cancer cells by regulating the expression of epithelial splicing regulatory protein 1 lead to promotion or suppression of lung metastasis without influencing cancer cell stemness. [Cell Death Dis] Full Article

NOS2 Expression in Glioma Cell Lines and Glioma Primary Cell Cultures: Correlation with Neurosphere Generation and SOX-2 Expression

Scientists investigated the inducible nitric oxide synthase (NOS)2 mRNA expression by reverse transcription-PCR in human glioma primary cultures and glioma stem cell derived neurospheres. Glioma cell lines were used as positive controls both in terms of stemness marker expression and that of capacity of generating neurospheres. The results showed that higher NOS2 expression was detected in all primary cultures that were able to form neurospheres. [Oncotarget] Full Article

IFN-γ Directly Inhibits Murine B-Cell Precursor Leukemia-Initiating Cell Proliferation Early in Life

The authors used the Eμ-ret transgenic mouse model of B-cell precursor acute lymphoblastic leukemia to assess the influence of IFN-γ on the early-life burden of leukemia-initiating cells. The absence of IFN-γ activity resulted in greater numbers of leukemia-initiating cells early in life and was associated with accelerated leukemia onset. [Eur J Immunol] Abstract

Effective and Persistent Antitumor Activity of HER2-Directed CAR-T Cells against Gastric Cancer Cells In Vitro and Xenotransplanted Tumors In Vivo

Researchers generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the gastric cancer cell antigen human epidermal growth factor receptor 2 (HER2), which harbors the CD137 and CD3ζ moieties. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. [Protein Cell] Full Article

Gli1 Expression in Cancer Stem-Like Cells Predicts Poor Prognosis in Patients with Lung Squamous Cell Carcinoma

Scientists aimed to reveal the clinical significance of glioma-associated oncogene homolog 1 (Gli1) in lung squamous cell carcinoma (LSCC) and investigate the potential of Gli1 as a cancer stem cell marker by comparing its expression with that of other stemness-related genes in LSCC. Gli1 expression was significantly correlated with T stage, lymph node metastasis, and clinical stage of LSCC. [Exp Mol Pathol] Abstract

Combination of Chemotherapy and Cancer Stem Cell Targeting Agents: Preclinical and Clinical Studies

Cancer stem cells possess a variety of phenotypes associated with therapeutic resistance and often cause recurrence of the diseases. The authors provide an updated discussion of these preclinical and clinical studies. [Cancer Lett] Abstract

A Unified Model of the Hierarchical and Stochastic Theories of Gastric Cancer

Scientists discuss existing evidence supporting a unified model of gastric cancer stem cells, including the regulatory mechanisms of this unified model in addition to the current status of stemness-related targeted therapy in gastric cancer patients. [Br J Cancer] Full Article

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

Stem Cell, Regenerative Medicine Leaders Join Forces to Advance Canada’s Position in the Field

Stem cell science is powering regenerative medicine. Leaders from across this emerging sector have joined forces to advance the field, through the newly created Regenerative Medicine Alliance of Canada (RMAC). RMAC will serve as a mechanism to support strategic activity across the regenerative medicine sector. Members will work collaboratively to share information and identify strategies that will benefit the growth of the sector. [University of Toronto] Press Release

Aprea Therapeutics Announces Research Collaboration with Memorial Sloan Kettering Cancer Center

Aprea Therapeutics announced a collaboration with Memorial Sloan Kettering Cancer Center to study the effects of reactivation of tumor suppressor protein p53 by APR-246. The goal of the collaboration is to evaluate and characterize preclinical efficacy of APR-246 in combination with multiple other anti-cancer agents and across multiple tumor types. [Aprea Therapeutics (PR Newswire Association LLC.)] Press Release

South Korea’s Scientists Seek Change amid Political Chaos

When South Korea’s Constitutional Court removed scandal-ridden President Park Geun-hye from office on 10^th March, citizens rejoiced in the streets — and many scientists breathed a sigh of relief. Her downfall has inspired a public appetite for broad governmental reforms, including changes in how the country supports scientific research. Many in the research community hope to end South Korea’s decades-long focus on applied research and shift more resources to basic science. [Nature News] Editorial

Ethical Guidelines on Lab-Grown Embryos Beg for Revamping, Scientists Say

Researchers in the U.K. and U.S. recently succeeded for the first time in growing embryos in the lab for nearly two weeks before terminating them, showing that the so-called 14-day rule is no longer a scientific limitation — although it remains a cultural one. Now, a group of Harvard University scientists has published a paper arguing that it is time to reconsider the 14-day rule because of advances in synthetic biology. [Scientific American] Editorial

Research Is an Afterthought in First Trump Budget

The 2018 budget proposal that President Donald Trump unveiled confirms two things that U.S. scientists have long suspected: The new president is no fan of research, and his administration has no overarching strategy for funding science. Deep proposed cuts to research at the National Institutes of Health, the Department of Energy, the U.S. Geological Survey, the Environmental Protection Agency, and the National Oceanic and Atmospheric Administration offer evidence that Trump doesn’t see science — of any kind — as a spending priority. [ScienceInsider] Editorial

NEW Biomed 2017: 22^nd International Biomedical Science & Technology Symposium
May 12-14, 2017
Ankara, Turkey, None

NEW ICoMI 2017: 1^st International Congress of Micro-Immunotherapy
May 18-20, 2017
Palma de Mallorca, Spain, None

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

NEW 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 Position – Stem Cell and Cancer Biology (Lund University)

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

Postdoctoral Fellow – Cancer Stem Cells (Boston Children’s Hospital/Harvard Medical School)

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

Research Fellow – Cancer and Stem Cell Biology (National University of Singapore)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

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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