Cancer Stem Cell News Volume 8.41 | Oct 23 2019

TOP STORY

Chronic Myelogenous Leukemia Stem Cells Require Cell-Autonomous Pleiotrophin Signaling

Chronic myelogenous leukemia (CML) stem cells upregulated expression of pleiotrophin (PTN) and required cell-autonomous PTN signaling for CML pathogenesis in BCR/ABL⁺ mice. Constitutive PTN deletion substantially reduced the numbers of CML stem cells capable of initiating CML in vivo. [J Clin Invest] Abstract | Full Article | Graphical Abstract

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The Mitochondrial Deoxyguanosine Kinase Is Required for Cancer Cell Stemness in Lung Adenocarcinoma

Scientists investigated the role of the deoxyguanosine kinase (DGUOK) in the self-renewal of lung cancer stem-like cells. Their data supported that DGUOK overexpression strongly correlated with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis, and cancer stem-like cell self-renewal. [EMBO Mol Med] Full Article

Radiation Drives the Evolution of Orthotopic Xenografts Initiated from Glioblastoma Stem-Like Cells

To determine the potential of radiotherapy to influence glioblastoma evolution, scientists used orthotopic xenografts initiated from CD133⁺ glioblastoma stem-like cells. Orthotopic xenografts grown in nude mice were exposed to a fractionated radiation protocol that resulted in a significant increase in animal survival. [Cancer Res] Abstract

In Silico Identification of Thiostrepton as an Inhibitor of Cancer Stem Cell Growth and an Enhancer for Chemotherapy in Non-Small-Cell Lung Cancer

Scientists used cancer-stem-cell-associated gene signatures to identify drug candidates that may inhibit cancer stem cell growth by reversing the cancer stem cell gene signature. Thiostrepton, a natural cyclic oligopeptide antibiotic, was the top-ranked candidate. [J Cell Mol Med] Full Article

Unbiased Peptoid Combinatorial Cell Screen Identifies Plectin Protein as a Potential Biomarker for Lung Cancer Stem Cells

To develop new approaches to detecting and targeting lung cancer stem cells, investigators applied an “unbiased” peptoid combinatorial cell screen to identify highly specific ligands that bound a cancer stem cell subpopulation of non-small cell lung cancer cells, but not the remaining aldefluor negative cancer cells from the same pre-clinical model. [Sci Rep] Full Article

Mithramycin A Inhibits Colorectal Cancer Growth by Targeting Cancer Stem Cells

Researchers showed for the first time that mithramycin A could successfully inhibit cancer stem cell proliferation, in addition to inhibiting bulk cancer cells in a model of colorectal cancer. A polymeric nanofiber scaffold culture system was established to develop 3D tumor organoids from cancer stem cell lines such as HT29, HCT116, KM12, CT26 and MC38 as well as ex vivo mouse tumors. [Sci Rep] Full Article

Hypoxia Induced Sonic Hedgehog Signaling Regulates Cancer Stemness, Epithelial-to-Mesenchymal Transition and Invasion in Cholangiocarcinoma

The authors investigated the relationship between hypoxia and Sonic Hedgehog (SHH) pathway activation and the effect of this interplay on cancer stemness and epithelial-to-mesenchymal transition during cholangiocarcinogenesis. Hypoxia promoted SHH pathway activation, evidenced by upregulated SHH and SMO levels, and enhanced glioma-associated oncogene homolog 1 nuclear translocation. [Exp Cell Res] Abstract

Bruceine D Inhibits Tumor Growth and Stem Cell-Like Traits of Osteosarcoma through Inhibition of STAT3 Signaling Pathway

Investigators explored the anti-osteosarcoma effects of bruceine D (BD), a natural compound derived from Brucea javanica, and investigated its underlying mechanisms. Results demonstrated that BD could significantly inhibit cell proliferation and migration, induce cell cycle arrest, and promote apoptosis in osteosarcoma cells. [Cancer Med] Full Article

Histone Methyltransferase SUV39H2 Regulates Cell Growth and Chemosensitivity in Glioma via Regulation of Hedgehog Signaling

Colony formation assays, CCK-8 assays, and flow cytometry were conducted to explore the role of SUV39H2 in the growth of glioma cells in vitro. A cell line-derived xenograft model was applied to explore SUV39H2’s role in U251 cell proliferation in vivo. Sphere formation assays, RT-qPCR, flow cytometry, and IF were conducted to illustrate the role of SUV39H2 in the stemness and chemosensitivity of glioma. [Cancer Cell Int] Full Article

Cross-Talk between Ribosome Biogenesis, Translation, and mTOR in CD133⁺ 4/CD44⁺ Prostate Cancer Stem Cells

CD133⁺ /CD44⁺ CSCs and non-CSCs were isolated from DU-145 cells using fluorescence-activated cell sorting. Researchers used Illumina HumanHT-12 v4 Expression to investigate gene expression profiling of cancer stem cells and non-cancer stem cells. Protein-protein interaction network analysis was performed using the STRING database. [Clin Transl Oncol] Abstract

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Dysregulated MicroRNA Fingerprints and Methylation Patterns in Hepatocellular Carcinoma, Cancer Stem Cells, and Mesenchymal Stem Cells

miRNAs constitute important epigenetic markers that regulate carcinogenesis by acting post-transcriptionally on mRNAs, contributing to the progression of hepatocellular carcinoma. The authors evaluate the available data concerning the epigenetic regulation of miRNAs through methylation and the possible role of this regulation in stem cell and somatic reprogramming in hepatocellular carcinoma. [Front Cell Dev Biol] Full Article

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Rafael Pharmaceuticals Enters into Collaboration with the National Institutes of Health (NIH) to Test CPI-613^® (Devimistat) in Cytokine Independent (Acute) HTLV-1 Associated Adult T-Cell Leukemia/Lymphoma

Rafael Pharmaceuticals, Inc. announced that it has entered into a collaboration with the National Cancer Institute (NCI), part of the NIH. This collaboration will test devimistat, Rafael’s first-in-class clinical lead compound, in cytokine independent human T-cell leukemia virus type 1 (HTLV-1) associated adult T-cell leukemia/lymphoma. [Rafael Pharmaceuticals, Inc. (GlobeNewswire, Inc.)] Press Release

UCLA Opens CAR T Clinical Trial Targeting Most Common Types of Lymphoma and Leukemia

The UCLA Jonsson Cancer Center has launched a pioneering chimeric antigen receptor (CAR) T cell immunotherapy trial that will attack cancer cells by simultaneously recognizing two targets – CD19 and CD20 – that are expressed on B-cell lymphoma and leukemia. [UCLA Jonsson Cancer Center] Press Release

Female Researchers in Australia Less Likely to Win Major Medical Grants than Males

Female scientists in Australia were less likely to win a major type of medical-research grants this year than their male counterparts, despite an overhaul of the country’s science funding that was supposed to address gender inequity. [Nature News] Editorial

Breaking: Trump Names Seven to Revived Presidential Science Advisory Panel

Thirty-three months after taking office, President Donald Trump has chosen a group of business leaders to advise him on science and technology policy. [ScienceInsider] Editorial

UK Science Minister Says DARPA-Like Agency Is in the Works

The UK government is working to establish a “blue sky” funding agency similar to the US Defense Advanced Research Projects Agency, UK science minister Chris Skidmore told the Science and Technology Select Committee of Parliament’s House of Commons. [ScienceInsider] Editorial

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NEW Postdoctoral Studentship – HOX Interactors for Leukemia (University of Manchester)

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