Cancer Stem Cell News Volume 7.27 | Jul 11 2018

TOP STORY

miR-196b Target Screen Reveals Mechanisms Maintaining Leukemia Stemness with Therapeutic Potential

Researchers used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. They found Cdkn1b (p27^Kip1) was a direct miR-196b target whose repression enhanced an embryonic stem cell-like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. [J Exp Med] Abstract | Press Release

(Ranked by impact factor of the journal)

Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-Like Cells

CD133⁺ glioblastoma cancer stem-like cells (GSC) exhibited reduced DNA replication velocity and a higher frequency of stalled replication forks than CD133- non-GSC in vitro. Exposure of non-GSC to low-level exogenous replication stress (RS) generated radiation resistance in vitro, confirming RS as a novel determinant of radiation resistance in tumor cells. [Cancer Res] Abstract | Full Article

SMAD4 Suppresses WNT-Driven De-Differentiation and Oncogenesis in the Differentiated Gut Epithelium

Investigators report a new condition in which tumors arise from the differentiated intestinal epithelium. Transcriptional profiling revealed acquisition of stem cell characteristics, and co-labeling indicated that cells expressing differentiated enterocyte markers entered the cell cycle and re-expressed stem cell genes upon simultaneous loss of SMAD4 and activation of the WNT pathway. [Cancer Res] Abstract

Tamoxifen Overrides Autophagy Inhibition in Beclin-1-Deficient Glioma Cells and their Resistance to Adenovirus-Mediated Oncolysis via Upregulation of PUMA and BAX

Scientists report that inhibition of autophagy in target glioma cells induced their resistance to killing by oncolytic agent CRAd-S-5/3. They found that downregulation of autophagy inducer Beclin-1 inhibited replication-competent oncolytic adenovirus-induced oncolysis of human glioma by suppressing cell proliferation and inducing premature senescence. [Oncogene] Abstract

Epigenetically Regulated PAX6 Drives Cancer Cells toward a Stem-Like State via GLI-SOX2 Signaling Axis in Lung Adenocarcinoma

PAX6 promoted GLI transcription, resulting in SOX2 upregulation directly by the binding of GLI to the proximal promoter region of the SOX2 gene. The overexpressed SOX2 enhanced the expression of key pluripotent factors and suppressed differentiation lineage factors, driving cancer cells toward a stem-like state. In contrast, in the differentiated non-cancer stem cells, PAX6 was transcriptionally silenced by its promoter methylation. [Oncogene] Abstract

BMP9 Counteracts the Tumorigenic and Pro-Angiogenic Potential of Glioblastoma

Investigators describe a strong bone morphogenetic protein 9 (BMP9)-mediated inhibition of the whole angiogenic process engaged during glioblastoma multiforme (GBM) tumor formation. BMP9 treatment was sufficient to induce a strong differentiation of GBM stem-like cells and to significantly counteract the already reported process of GBM cell transdifferentiation into tumor-derived endothelial cells not only in in vitro mimicked tumor-derived endothelial cell models, but also in vivo in orthotopic xenografts in mice. [Cell Death Differ] Abstract

miR-34a Exerts as a Key Regulator in the Dedifferentiation of Osteosarcoma via PAI-1-Sox2 Axis

Inhibition of miR-34a promoted the reprogramming transition of osteosarcoma (OS). Exploration on the downstream network of miR-34a identified that blocking plasminogen activator inhibitor-1 (PAI-1) expression could restrain OS dedifferentiation into cancer stem-like cells by downregulating SRY-related-HMG box (Sox) 2. [Cell Death Dis] Full Article

Transcriptome Profiling of Panc-1 Spheroid Cells with Pancreatic Cancer Stem Cell Properties Cultured by a Novel 3D Semi-Solid System

Researchers optimized an existing culture system by adding methylcellulose to create a 3D semi-solid system which prevented non-specific aggregation. They identified the CSC properties of Panc-1 spheroid cells cultured by this system by detecting the genes associated with stemness and by evaluation of the tumorigenicity in vitro and in vivo through invasion, migration and xenograft experiments methods. [Cell Physiol Biochem] Full Article

miR-137 Suppresses Triple-Negative Breast Cancer Stemness and Tumorigenesis by Perturbing BCL11A-DNMT1 Interaction

In both SUM149 and MDA-MB-231 cells, overexpression of miR-137 or knockdown of B-cell lymphoma/leukemia 11A (BCL11A) reduced the number of tumoroshperes and the percentage of cancer stem cells in vitro, and inhibited tumor development in vivo. BCL11A interacted with DNA methyltransferases 1 (DNMT1) in triple negative breast cancer (TNBC) cells. Silencing of either BCL11A or DNMT1 impaired cancer stemness and tumorigenesis of TNBC via suppressing Islet-1 expression both in vitro, and in vivo. [Cell Physiol Biochem] Full Article

Cargo-Free Nanomedicine with pH Sensitivity for Codelivery of DOX Conjugated Prodrug with SN38 To Synergistically Eradicate Breast Cancer Stem Cells

Through the intermolecular interaction between DOX and SN38, PEG-CH═N-DOX and SN38 were assembled together to form a stable nanomedicine. This nanomedicine not only dramatically enhanced drug accumulation efficiency at the tumor site but also effectively eliminated breast CSCs (bCSCs) and non-bCSCs, which resulted in achieving a superior in vivo tumor inhibition activity. [Mol Pharm] Abstract | Graphical Abstract

Nitric Oxide Promotes Cancer Cell Dedifferentiation by Disrupting an Oct4: Caveolin-1 Complex: A New Regulatory Mechanism for Cancer Stem Cell Formation

Investigators found that nitric oxide (NO) directly affected the stability and function of octamer-binding transcription factor 4 (Oct4), know to drives the stemness of lung cancer cells. They demonstrated that NO promoted the CSC-regulatory activity of Oct4 through a mechanism that involves complex formation between Oct4 and the scaffolding protein caveolin-1. [J Biol Chem] Abstract | Full Article

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EMT, Stemness and Tumor Plasticity in Aggressive Variant Neuroendocrine Prostate Cancers

The authors examine the contributions of epithelial-to-mesenchymal transition (EMT)-induced cellular-plasticity and stem-cell signaling pathways to the progression of neuroendocrine/aggressive variant prostate cancers in the light of potential therapeutic opportunities. [Biochim Biophys Acta] Abstract

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BioSight Launches a Phase IIb Clinical Trial of BST-236 as a First-Line Treatment of Acute Myeloid Leukemia

BioSight Ltd. announced that it has received the FDA and the Israeli Ministry of Health clearance to launch a Phase IIb clinical trial of BST-236 for treatment of acute myeloid leukemia. [BioSight Ltd. (PR Newswire Association LLC)] Press Release

European Commission Approves Expanded Indication for Sprycel (Dasatinib) to Include Treatment of Children with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase

Bristol-Myers Squibb Company announced that the European Commission has expanded the indication for Sprycel (dasatinib) to include the treatment of children and adolescents aged 1 year to 18 years with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase, and to include a powder for oral suspension formulation. [Bristol-Myers Squibb] Press Release

Loyola to Pursue NCI Comprehensive Cancer Center Designation

Loyola Medicine’s Cardinal Bernardin Cancer Center and Loyola University Chicago Stritch School of Medicine are expanding their renowned cancer program to advance the pursuit of National Cancer Institute designation as a Comprehensive Cancer Center. As a major part of this initiative, Stritch is launching a new Department of Cancer Biology to study cancer at the molecular level. [Loyola Medicine] Press Release

Goethe University Awarded Funds for New Cancer Research Institute Including New Building

Goethe University has a new LOEWE Centre under its belt – together with its own research building that is planned for completion by 2023. A good € 73.4 million are being made available for this purpose; the decision followed a recommendation by the German Council of Science and Humanities in April 2018. [Goethe-Universität Frankfurt am Main] Press Release

Chinese Researchers to Get More Autonomy Over Lab Spending

Chinese Premier Li Keqiang says the country will ease restrictive rules governing how research funds are used, and cut red tape for researchers. Revised rules are designed to help researchers focus on their work and compete with their counterparts globally. [Nature News] Editorial

UK Universities Fall Short on Reporting Misconduct Investigations

The United Kingdom should establish a committee to monitor efforts by the nation’s universities to properly conduct misconduct investigations, a parliamentary inquiry recommends. The guidance follows a new report released on 11 July, revealing that one in four UK universities does not comply with research integrity guidelines released six years ago. [Nature News] Editorial

Research Charity Launches $330M Initiative to Fund High-Risk Life Sciences Projects

One of the world’s largest biomedical research charities is setting up a new $330 million initiative to fund high-risk projects — an effort it hopes can help researchers challenge the status quo in the life sciences. [STAT] Editorial

Foreign-Researcher Figures Stress Need for Immigration Reform Before Brexit

The UK immigration system may need to process tens of thousands more visas for scientists each year if European Union citizens lose their special immigration rights after Brexit, figures obtained by Nature suggest. The numbers underscore the urgent need for reform of the rules governing immigration for researchers — a topic that a parliamentary group has been investigating since May. [Nature News] Editorial

NEW International Society for Stem Cell Research (ISSCR) 2019 Annual Meeting
June 26-29, 2019
Los Angeles, California, United States

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

NEW Postdoctoral Scholar – Statistical Bioinformatics (The University of Iowa)

NEW Postdoctoral Positions – Gene Regulation and/or Cancer Biology (University of North Carolina at Chapel Hill School of Medicine)

NEW Postdoctoral Researcher – Cancer Stem Cells and Epitranscriptomics (University of California San Diego)

NEW Postdoctoral Fellowship – Structure-Based Studies for a Search of New Drug Leads for Leukemia Treatment (European Molecular Biology Laboratory)

Postdoctoral Scientist – Drug Discovery & Cancer Stem Cell Biology (Cancer Research UK Manchester Institute)

Postdoctoral Fellow – Cancer Biology (Children’s Cancer Therapy Development Institute)

Postdoctoral Training Fellow – Breast Cancer Stem Cells (The Francis Crick Institute)

Tenure-Track Faculty Positions – Various (The Ohio State University)

Postdoctoral Fellow – Stem Cell Biology and Pharmacogenomics (Northwestern University Feinberg School of Medicine)

PhD Student – Cell Signaling (German Cancer Research Center)

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