Cancer Stem Cell News Volume 6.40 | Oct 11 2017

TOP STORY

Targeting Glioma Stem Cells through Combined BMI1 and EZH2 Inhibition

Using both genetic and pharmacologic inhibition, scientists found that proneural glioma stem cells (GSCs) were preferentially sensitive to EZH2 disruption, whereas mesenchymal GSCs were more sensitive to BMI1 inhibition. Given that glioblastomas contained both proneural and mesenchymal GSCs, combined EZH2 and BMI1 targeting proved more effective than either agent alone both in culture and in vivo. [Nat Med] Abstract

(Ranked by impact factor of the journal)

Synthesis and Anti-Pancreatic Cancer Stem Cell Activity of BE-43547A₂

Researchers found that BE-43547A₂ can significantly reduce the percentage of pancreatic cancer stem cells in Panc-1 cells, and dramatically ablate the tumorsphere forming capability of Panc-1 cells. The tumor-initiating assay in vivo confirmed that BE-43547A₂ could abolish the tumorigenesis of Panc-1 cells. [Angew Chem Int Ed Engl] Abstract

PAF Promotes Stemness and Radioresistance of Glioma Stem Cells

An integrated genomic and functional analysis to elucidate DNA damage signaling factors promoting self-renewal of glioma stem cells (GSCs) identified proliferating cell nuclear antigen-associated factor (PAF) up-regulation in glioblastoma. [Proc Natl Acad Sci USA] Abstract

Transcriptional Memory of Cells of Origin Overrides β-Catenin Requirement of MLL Cancer Stem Cells

While β‐catenin has been demonstrated as an essential molecule and therapeutic target for various CSCs including those driven by MLL fusions, researchers show that transcriptional memory from cells of origin predicts acute myeloid leukemia patient survival and allows β‐catenin‐independent transformation in MLL‐CSCs derived from hematopoietic stem cell‐enriched Lin^–Sca-1+c-kit⁺ population but not myeloid–granulocyte progenitors. [EMBO J] Abstract

Brachyury-YAP Regulatory Axis Drives Stemness and Growth in Cancer

Scientists showed that brachyury was a crucial regulator of stemness in chordoma and in more common aggressive cancers. Furthermore, this effect of brachyury was mediated by control of synthesis and stability of Yes-associated protein (YAP), a key regulator of tissue growth and homeostasis, providing an unexpected mechanism of control of YAP expression. [Cell Rep] Abstract

Essential Role of METTL3-Mediated m⁶A Modification in Glioma Stem-Like Cells Maintenance and Radioresistance

Investigators report the crucial role of methyltransferase-like 3 (METTL3)-mediated m⁶A modification in glioma stem-like cells (GSC) maintenance and dedifferentiation of glioma cells. METTL3 expression was elevated in GSC and attenuated during differentiation. [Oncogene] Abstract

Resistin Facilitates Breast Cancer Progression via TLR4-Mediated Induction of Mesenchymal Phenotypes and Stemness Properties

Resistin was found to promote epithelial–mesenchymal transition and stemness in breast cancer cells—mechanisms critical to tumorigenesis and metastasis—through a toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells/signal transducer and activator of transcription 3 signaling pathway and negated by TLR4-specific antibody and antagonist. [Oncogene] Abstract

FAT1 Modulates EMT and Stemness Genes Expression in Hypoxic Glioblastoma

The authors identified the role of FAT1 in regulating epithelial-mesenchymal transition (EMT) and stemness characteristics in glioblastoma (GBM). The expression of FAT1, EMT (Snail/LOX/Vimentin/N-cad), stemness (SOX2/OCT4/Nestin/REST) and hypoxia markers (HIF-1α/VEGF/PGK1/CA9) was upregulated in ≥39% of GBM tumors with significant positive correlation of the expression of FAT1 with LOX/Vimentin/SOX2/HIF-1α/PGK1/VEGF/CA9. [Int J Cancer] Abstract

Curcumin Reversed Chronic Tobacco Smoke Exposure Induced Urocystic EMT and Acquisition of Cancer Stem Cells Properties via Wnt/β-Catenin

Researchers investigated the role of Wnt/β-catenin pathway in chronic tobacco smoke (TS) exposure induced urocystic epithelial–mesenchymal transition (EMT), stemness acquisition and the preventive effect of curcumin. Long time TS exposure induced EMT changes and the levels of CSCs’ markers were significant upregulated. [Cell Death Dis] Full Article

Protein and Chemotherapy Profiling of Extracellular Vesicles Harvested from Therapeutic Induced Senescent Triple Negative Breast Cancer Cells

Investigators profiled extracellular vesicles harvested from therapeutic induced senescent (TIS) triple negative breast cancer (TNBC) cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy. [Oncogenesis] Full Article

Cancer Stem Cells Revisited

Scientists discuss new developments in the CSC field in relationship to changing insights into how normal stem cells maintain healthy tissues. Expectations in the field have become more realistic, and now, the first successes of therapies based on the CSC concept are emerging. [Nat Med] Abstract

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

Medicenna Presents Clinical Data on Initial Experience from Ongoing Phase IIb Study of MDNA55

Medicenna Therapeutics Corp. announced that new clinical data demonstrated successful delivery in brain cancer patients and a reassuring safety profile for MDNA55, the company’s lead immunotherapeutic agent targeting the interleukin-4 receptor. [Press release from Medicenna Therapeutics Corp. discussing research presented at the 2017 Congress of Neurological Surgeons, Boston] Press Release

FDA Awards 15 Grants for Clinical Trials to Stimulate Product Development for Rare Diseases

The FDA announced that it has awarded 15 new clinical trial research grants totaling more than $22 million over the next four years to boost the development of products for patients with rare diseases. [U.S. Food and Drug Administration] Press Release

U.S. FDA Grants Fast Track Designation to Astellas for Development of Gilteritinib in Relapsed or Refractory Acute Myeloid Leukemia

Astellas Pharma Inc. announced that the FDA has granted Fast Track designation for the development of gilteritinib for adult patients with FLT3 mutation-positive relapsed or refractory acute myeloid leukemia. [Astellas Pharma Inc.] Press Release

FDA Grants Orphan Drug Designation to Trovagene’s PLK1 Inhibitor, PCM-075, for the Treatment of Acute Myeloid Leukemia (AML)

Trovagene, Inc. announced that the FDA granted an orphan drug designation to PCM-075 for the treatment of patients with AML. PCM-075 is an oral, highly-selective adenosine triphosphate competitive inhibitor of the serine/threonine Polo-like Kinase 1 (PLK1) enzyme, which appears to be over expressed in several different hematologic malignancies and solid tumor cancers. [Trovagene, Inc.] Press Release

Publishers Threaten to Remove Millions of Papers from ResearchGate

Millions of articles might soon disappear from ResearchGate, the world’s largest scholarly social network. Five publishers said they had formed a coalition that would start ordering ResearchGate to remove research articles from its site because they breach publishers’ copyright. [Nature News] Editorial

Navajo Nation Reconsiders Ban on Genetic Research

When the Navajo Nation opens its first oncology center next year in Tuba City, Arizona, clinicians there may be able to offer a service that has been banned on tribal lands for 15 years: analyzing the DNA of Navajo tribe members to guide treatments and study the genetic roots of disease. [Nature News] Editorial

Does Your State Get Its Fair Share of Federal Research Dollars?

The only physicist in Congress has introduced a bill that could rekindle a debate over how to deal with geographic disparities in the allocation of federal research funding [ScienceInsider] Editorial

Scientists Plead with Brazilian Government to Restore Funding

Anxiety is growing in Brazil over the country’s collapsing research budgets. President Michel Temer had slashed funding for science by 44% and has proposed additional decreases for 2018 — even as some science institutes run out of money for basic needs, such as paying electricity bills. The 2017 science budget, at 3.2 billion reais (US$1 billion), is the lowest the country has seen in at least 12 years. [Nature News] Editorial

NEW 25^th Biennial Congress of the European Association for Cancer Research (EACR)
June 30-July 3, 2018
Amsterdam, Netherlands

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

NEW Scientist – Tumour Microenvironment and Cancer Stem Cells (Evotec Toulouse)

Postdoctoral Fellow – Leukemia Stem Cells (Memorial Sloan Kettering Cancer Center)

Assistant Professor – Cancer Biology (Perelman School of Medicine)

Assistant Professor – Cancer Research (University of Minnesota)

Postdoctoral Fellow – Cancer Stem Cell Research (MD Anderson Cancer Center)

Postdoctoral Positions – Stem Cell and Cancer Biology (Johns Hopkins University)

Director – Stanford Cancer Institute (Stanford University)

Faculty Position – Stem Cell Biology (University of Texas Southwestern Medical Center)

Faculty Positions – Cancer and Stem Cell Biology (Sun Yat-Sen University)

Postdoctoral Fellows – Cancer Stem Cell Biology (Genome Institute of Singapore)

Research Officers – Cancer Stem Cell Biology (Genome Institute of Singapore)

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