Cancer Stem Cell News Volume 8.22 | Jun 12 2019

TOP STORY

SIRT1 Regulates Metabolism and Leukemogenic Potential in CML Stem Cells

Scientists identified a previously unrecognized role for sirtuin 1 (SIRT1) in mediating increased mitochondrial oxidative phosphorylation in chronic myeloid leukemia (CML) leukemia stem cells. They showed that mitochondrial alterations were kinase independent and that tyrosine kinase inhibitor treatment enhanced inhibition of CML hematopoiesis in SIRT1-deleted mice. [J Clin Invest] Full Article | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Lineage Tracing and Targeting of IL17RB⁺ Tuft Cell-Like Human Colorectal Cancer Stem Cells

Investigators showed that IL17RB marked intestinal tumor stem cells in an IL13-dependent manner. Tuft cell-like cancer cells were detected in a subset of human colorectal cancers (hCRCs). In these hCRCs, lineage-tracing experiments in CRISPR-Cas9-mediated IL17RB-CreERT2 knockin organoids and xenograft tumors revealed that IL17RB marked CSCs that expanded independently of IL-13. [Proc Natl Acad Sci USA] Abstract

An ERG Enhancer-Based Reporter Identifies Leukemia Cells with Elevated Leukemogenic Potential Driven by ERG-USP9X Feed-Forward Regulation

Researchers utilized a genetic reporter which assessed stemness to enrich and functionally characterize leukemia stem cells. They observed heterogeneous activity of the ERG+85 enhancer-based fluorescent reporter in human leukemias. Cells with high reporter activity (tagBFPHigh) exhibited elevated expression of stemness and chemoresistance genes and demonstrated increased clonogenicity and resistance to chemo- and radiotherapy as compared to their tagBFPNeg counterparts. [Cancer Res] Abstract

Down-Regulated LncRNA DLX6-AS1 Inhibits Tumorigenesis through STAT3 Signaling Pathway by Suppressing CADM1 Promoter Methylation in Liver Cancer Stem Cells

The silencing of long non-coding RNA (lncRNA) DLX6-AS1 was shown to reduce and inhibit spheroid formation, colony formation, proliferation, and tumor formation abilities, as well as attenuate CD133, CD13, OCT-4, SOX2, and Nanog expression in liver cancer stem cells. [J Exp Clin Cancer Res] Full Article

Evolution of Nucleic Acid Aptamers Capable of Specifically Targeting Glioma Stem Cells via Cell-SELEX

Early detection and targeted therapy of glioma stem cells (GSCs) may significantly improve the survival rate of glioma patients. Therefore, molecular ligands capable of selectively recognizing GCSs are of great importance. In this work, the authors successfully generated a group of DNA aptamers that specifically recognized GSCs via Cell-SELEX technology. [Anal Chem] Abstract

A New Label-Free Approach to Glioblastoma Cancer Stem Cell Sorting and Detection

Scientists developed a new label-free methodology to isolate, enrich, and identify CSCs from an heterogeneous tumor cell subpopulation using a cell sorting method and a biosensor as a detector. Enrichment was optimized using an original protocol and U87-MG glioblastoma cells cultured in normal (N) or defined (D) medium under normoxic (N) or hypoxic (H) conditions to obtain four cell populations: NN, NH, DN, and DH. [Anal Chem] Abstract

miR-340-5p Suppresses Aggressiveness in Glioblastoma Multiforme by Targeting Bcl-W and Sox2

Bcl-w and PDGF-A levels were positively regulated and increased tumorigenicity by Sox2 activation in glioblastoma multiforme (GBM) cells. miR-340-5p was further identified as a direct inhibitor of Bcl-w and Sox2. Overexpression of miR-340-5p reduced mesenchymal traits, cell migration, invasion, and stemness in GBM through attenuating Bcl-w and Sox2 expression. [Mol Ther Nucleic Acids] Abstract | Full Article

Arsenic Trioxide Inhibits Liver Cancer Stem Cells and Metastasis by Targeting SRF/MCM7 Complex

Investigators demonstrated that arsenic trioxide (ATO) inhibited tumorigenesis and distant metastasis in mouse models, corresponding with prolonged mice survival time. Also, ATO was found to significantly decrease the CSC-associated traits. Moreover, minichromosome maintenance protein 7 (MCM7) knockdown recapitulated the effects of ATO on CSCs and metastasis, while ectopic expression of MCM7 abolished them. [Cell Death Dis] Full Article

INPP4B Exerts a Dual Function in the Stemness of Colorectal Cancer Stem-Like Cells through Regulating Sox2 and Nanog Expression

Inositol polyphosphate 4-phosphatase type II (INPP4B) overexpression inhibited self-renewal, and chemoresistance of primary non-metastatic colorectal cancer stem-like cells (CR-CSLCs), but exerted the opposite roles in highly metastatic CR-CSLCs in vitro. Similarly, INPP4B knockdown had dual functions in the self-renewal and chemoresistance of different CR-CSLCs. [Carcinogenesis] Abstract

AGR2 Is a Target of Canonical Wnt/β-Catenin Signaling and Is Important for Stemness Maintenance in Colorectal Cancer Stem Cells

Researchers found that anterior gradient 2 (AGR2) was a novel stem cell marker that was regulated by the canonical Wnt/β-catenin pathway in colon CSCs. AGR2 was highly co-expressed with surface stem cell markers in spheroidal culture. Silencing of AGR2 resulted in decreased sphere-forming ability and down-regulated expression of stem cell markers, whereas the opposite effects were seen with AGR2 overexpression. [Biochem Biophys Res Commun] Abstract

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Clinical and Therapeutic Implications of Cancer Stem Cells

Like normal tissues, cancers can replenish themselves, grow, and metastasize because of stem cells that are similar to normal stem cells but seem to respond less well to environmental stop signals in their niche. Therapy that targets cancer stem cells may be the next avenue of cancer treatment. [N Engl J Med] Abstract

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Pediatric CAR T-Cell Immunotherapy Trial Aims to Improve Remission Rates of Leukemia at Children’s National Health System

Children’s National Health System announced the opening of a unique chimeric antigen receptor (CAR) T-cell immunotherapy trial for pediatric patients with relapsed positive acute lymphoblastic leukemia. The PLAT-05 trial will focus on targeting the CD19 and CD22 proteins simultaneously found in leukemia cancer cells. [Children’s National Health System (PR Newswire Association LLC.)] Press Release

MetVital, Inc. Announces FDA Clearance of Investigational New Drug (IND) Application for AEO for Phase II Testing for Glioblastoma Multiforme

MetVital, Inc. announced that the FDA has notified MetVital that it may proceed with its clinical investigation of “Anhydrous Enol-Oxaloacetate” (AEO) as a potential treatment for patients with glioblastoma multiforme. The notice to proceed was received following MetVital’s submission of an IND application for this program. FDA has approved a Phase IIA “Proof of Concept” trial to advance. [MetVital, Inc.] Press Release

OSE Immunotherapeutics Receives US Patent Notice of Allowance for Use of Tedopi^® to Treat Brain Metastasis

OSE Immunotherapeutics announced that the United States Patent and Trademark Office has issued the notice of allowance for a new patent family related to Tedopi^®, for use in the treatment of brain metastasis originating from cancers, including non-small cell lung cancer, in HLA-A2 positive patients. [OSE Immunotherapeutics] Press Release

UCLA Professor’s Last Gift Will Support Research in Cancer and Stem Cell Biology

The gift established the Doumani Research Innovation Fund, which will support the work of faculty affiliated with the Broad Stem Cell Research Center and the UCLA Jonsson Comprehensive Cancer Center who are conducting multidisciplinary research aimed at translating scientific discoveries into new treatments for people with cancer. [Reagents of University of California] Press Release

Sudanese Academics Defiant as Revolution Turns Bloody

Sudan’s universities are shut, flights have been suspended and the Internet remains almost entirely blocked after a brutal crackdown in which paramilitaries are thought to have killed some 100 pro-democracy protestors. But none of this has dented the resolve of the protestors, whose ranks include several prominent academics and whose demands include freeing universities from government influence. [Nature News] Editorial

Wellcome Sanger Institute to Close Animal Facility

The Wellcome Sanger Institute announced that it would be closing its animal facility, which provides mice, zebrafish, rats, and frogs to geneticists at the institute and internationally, reports Nature. The institute states that the closure is related to the growing use of cell lines and organoids, instead of animals. [The Scientist] Editorial

NEW Society for Immunotherapy of Cancer (SITC) 2019
November 6-10, 2019
National Harbor, Maryland, United States

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NEW Postdoctoral Fellow – Jak-Stat Signaling in Prostate & Pancreatic Cancer (Medical College of Wisconsin)

Tier I Canada Research Chair – Precision & Molecular Oncology (University of Calgary)

Postdoctoral Scholar – Pediatric Hematology/Oncology (Pennsylvania State University)

Faculty Positions – Cancer Research (The University of Texas MD Anderson Cancer Center)

Postdoctoral Position – Cancer Biology (Washington University School of Medicine)

BIH Johanna Quand Professorships for Women Scientists – Open Topic (Stiftung Charité and The Berlin Institute of Health)

Postdoctoral Fellow Position – Stem Cells in Colon Cancer (Vanderbilt University Medical Center)

Postdoctoral Position – Tumor Metabolism, Stem Cell Biology & Circadian Clock Distruption (University of California Irvine)

Principal Investigator – Cancer Research (Zhejiang University)

Research Associates – Cell Competition in Cancer (University of Bristol)

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