Cancer Stem Cell News Volume 8.31 | Aug 14 2019

TOP STORY

Targeting Pyrimidine Synthesis Accentuates Molecular Therapy Response in Glioblastoma Stem Cells

Researchers traced metabolic aberrations in glioblastoma stem cells (GSCs) to link core genetic mutations in glioblastoma to dependency on de novo pyrimidine synthesis. Targeting the pyrimidine synthetic rate-limiting step enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase or the critical downstream enzyme dihydroorotate dehydrogenase inhibited GSC survival, self-renewal, and in vivo tumor initiation through the depletion of the pyrimidine nucleotide supply in rodent models. [Sci Transl Med] Abstract | Press Release

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Autophagy Inhibition Elicits Emergence from Metastatic Dormancy by Inducing and Stabilizing Pfkfb3 Expression

Scientists observed an inverse relationship between 6-phospho-fructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) expression and autophagy, which reduced Pfkfb3 expression and elicited cellular dormancy. Targeted depletion of Atg3, Atg7, or p62/sequestosome-1 to inactivate autophagy restored aberrant Pfkfb3 expression in dormant breast cancer stem cells, leading to their reactivation of proliferative programs and outgrowth. [Nat Commun] Full Article

Combined Inhibition of MDM2 and Bcr-Abl Tyrosine Kinase Targets Chronic Myeloid Leukemia Stem/Progenitor Cells in a Murine Model

Using an inducible transgenic Scl-tTa-BCR-ABL1 murine chronic myeloid leukemia model, investigators found, by RT-PCR and CyTOF proteomics, increased p53 signaling in chronic myeloid leukemia bone marrow cells compared with controls in CD45⁺ and linage-SCA-1+C-KIT⁺ populations. Chronic myeloid leukemia bone marrow cells were more sensitive to exogenous BH3 peptides than controls. [Haematologica] Abstract | Full Article

Glioma-Associated Human Endothelial Cell-Derived Extracellular Vesicles Specifically Promote the Tumorigenicity of Glioma Stem Cells via CD9

The authors showed that glioma-associated human endothelial cells, a main component of the perivascular niche, released extracellular vesicles (EVs) that increased glioma stem cell (GSC) proliferation and tumor-sphere formation. GSCs treated with GhEC-EVs created a significantly greater tumor burden than do untreated GSCs in orthotopic xenografts. [Oncogene] Abstract

Regulatory Networks in Mechanotransduction Reveal Key Genes in Promoting Cancer Cell Stemness and Proliferation

Scientists evaluated the transcriptome alteration during tumor-repopulating cells (TRCs) generation in 3D culture and revealed that a variety of molecules related with integrin/membrane and stemness were continuously altered by mechanical environment. Some key regulators such as MYC/STAT3/hsa-miR-199a-5p, were changed in the TRCs generation. [Oncogene] Full Article

Deacetylation of β-Catenin by SIRT1 Regulates Self-Renewal and Oncogenesis of Liver Cancer Stem Cells

Mechanistically, researchers showed that nuclear accumulation of β-catenin resulted from deacetylation mediated by SIRT1. Further, nuclear β-catenin promoted the transcription of Nanog to help maintain self-renewal of liver cancer stem cells. [Cancer Lett] Abstract

Folate Can Promote the Methionine-Dependent Reprogramming of Glioblastoma Cells towards Pluripotency

Data showed that for all cell lines studied, exogenous methionine was required for tumor sphere (TS) formation but not for monolayer (ML) cells proliferation. Furthermore, for glioblastoma cell lines, regardless of the addition of folate cycle substrates, the level of 3 folate isoforms, 5-methytetrahydrofolate, 5,10-methenyltetrahydrofolate, and 10-formyltetrahydrofolate were all downregulated in TS relative to ML cells [Cell Death Dis] Full Article

The Hippo Effector TAZ Promotes Cancer Stemness by Transcriptional Activation of SOX2 in Head Neck Squamous Cell Carcinoma

Researchers identified sex determining region Y box 2 (SOX2) as a putative downstream target of TAZ to promote CSCs maintenance and tumorigenicity in head neck squamous cell carcinoma. Both TAZ and SOX2 were significantly enriched in CSCs subpopulation isolated from Cal27 and Fadu cells via fluorescence-activated cell sorting. [Cell Death Dis] Full Article

BMP-4 Enhances Epithelial Mesenchymal Transition and Cancer Stem Cell Properties of Breast Cancer Cells via Notch Signaling

BMP-4 enhanced epithelial mesenchymal transition (EMT) and stem cell properties in both mammary epithelial cell line and breast carcinoma cell line. BMP-4 increased the expression of EMT biomarkers, such as fibronectin, laminin, N-cadherin, and Slug. [Sci Rep] Full Article

Identification of Key Candidate Targets and Pathways for the Targeted Treatment of Leukemia Stem Cells of Chronic Myelogenous Leukemia Using Bioinformatics Analysis

Investigators identified 51 differentially expressed microRNAs through integrated analysis of GSE90773 and performed functional gene predictions for microRNAs. Then, GSE11889 and GSE11675 were integrated to obtain differentially expressed genes (DEGs), and the overlapping DEGs were used as models to identify predictive functional genes. [Mol Genet Genomic Med] Full Article

The Effects of Tramadol on Cancer Stem Cells and Metabolic Changes in Colon Carcinoma Cells Lines

Scientists used Colo320, Colo741 and HCT116 colon cancer cell lines. CD133 was considered colon cancer stem cell marker and used to sort CD133⁺ and CD133⁻ cells by magnetic cell sorting. Mitochondria-targeted therapeutics technique was used to detect tramadol’s cytotoxic effect on cells in the study groups. [Gene] Abstract

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EMT and Stemness-Key Players in Pancreatic Cancer Stem Cells

CSCs are a subpopulation of cancer cells with stem-like features that are responsible for the propagation of the tumor as well as therapy resistance and cancer relapse, but also for circulating tumor cell release and metastasis. In support of this concept, epithelial-to-mesenchymal transition (EMT) transcription factors generate cells with stem cell properties and mediate chemoresistance. [Cancers] Full Article

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CLR 131 Advances to Second Malignant Brain Tumor Cohort of Ongoing Pediatric Phase I Study

Cellectar Biosciences, Inc. announced it has successfully completed the first cohort of malignant brain tumor patients in its ongoing Phase I trial of CLR 131 in children and adolescents with select solid tumors, lymphoma, and malignant brain tumors, including relapsed or refractory neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma, and osteosarcoma. [Cellectar Biosciences, Inc.] Press Release

KIYATEC Announces Addition of Capital Health as Clinical Site in Trial to Predict GBM Patient-Specific Response to Cancer Drugs Prior to Treatment

KIYATEC, Inc. announced that Capital Health has joined its US clinical trial, 3D-PREDICT, to validate the company’s test as a patient-specific predictor of response to cancer therapies in glioblastoma (GBM) and anaplastic astrocytoma patients. [KIYATEC, Inc.] Press Release

Calquence Granted US Breakthrough Therapy Designation for Chronic Lymphocytic Leukemia

AstraZeneca announced that the FDA has granted Breakthrough Therapy Designation for Calquence as a monotherapy treatment for adult patients with chronic lymphocytic leukemia. [AstraZeneca] Press Release

Ziopharm Oncology Receives Positive Opinion for Orphan Drug Designation from the European Medicines Agency for Ad-RTS-hIL-12 Plus Veledimex for the Treatment of Glioma

Ziopharm Oncology, Inc. announced the European Medicines Agency Committee for Orphan Medicinal Products adopted a positive opinion recommending Ad-RTS-hIL-12 plus veledimex for designation as an orphan medicinal product for the treatment of glioma. [Ziopharm Oncology, Inc.] Press Release

Janssen Announces European Commission Approval of Imbruvica^®▼(ibrutinib) for Expanded Use in Two Indications

The Janssen Pharmaceutical Companies of Johnson & Johnson announced that the European Commission has approved variations to broaden the use of Imbruvica^® in two indications. This includes the use of ibrutinib in combination with obinutuzumab in adult patients with previously untreated chronic lymphocytic leukaemia and the use of ibrutinib plus rituximab for the treatment of adult patients with Waldenström’s macroglobulinemia. [The Janssen Pharmaceutical Companies of Johnson & Johnson] Press Release

Novartis Ousted Top Scientists over Manipulation of Data for Gene Therapy

Novartis dismissed the top two scientists at its gene therapy division shortly after CEO Vas Narasimhan learned of internal data falsification that has since snowballed into a damaging scandal. [STAT New] Editorial

UC Faculty Members Quit Cell Press Editorial Boards over Impasse with Publisher

Some of the University of California’s (UC’s) most prominent scientists have announced they will resign from editorial boards of Cell Press to protest the continuing impasse between its owner, publishing giant Elsevier, and UC over subscription costs and open access to articles. [ScienceInsider] Editorial

Academia to FBI on Monitoring Chinese Scientists: “Tread Carefully”

Nearly two dozen higher education groups warn the government to be cautious when advising US research universities to keep an eye on students and faculty with ties to certain Chinese institutions. [The Scientist] Editorial

NEW From Stem Cell Biology to New Therapies
November 6-8, 2019
Toronto, Ontario, Canada

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NEW Assciate Professor – Immunology (Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai)

NEW Postdoctoral Scientist – Cancer and Luekemia (St. Jude Children’s Research Hospital)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctral Fellow – Leukemic Stem Cell Biology (McGill University Health Centre)

Postdoctoral Researcher – Cancer Stem Cells in Glioblastoma (The Institut Curie Research Center)

Postdoctoral Associate – Hematopoietic Stem Cells and Leukemia (The Jackson Laboratory)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Research Scientist – Leukemia Stem/Progenitor Cell Research (MD Anderson Cancer Center)

Postdoctoral Scientist – Cancer Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

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