Cancer Stem Cell News Volume 8.35 | Sep 11 2019

TOP STORY

The Transcribed Pseudogene RPSAP52 Enhances the Oncofetal HMGA2-IGF2BP2-RAS Axis through LIN28B-Dependent and Independent let-7 Inhibition

The authors found that the oncofetal HMGA2 gene was aberrantly re-expressed in many tumor types together with its antisense transcribed pseudogene RPSAP52. RPSAP52 was abundantly present in the cytoplasm, where it interacted with the RNA binding protein IGF2BP2/IMP2, facilitating its binding to mRNA targets, promoting their translation by mediating their recruitment on polysomes and enhancing proliferative and self-renewal pathways. [Nat Commun] Full Article | Press Release

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Discovery of a New Pyrimidine Synthesis Inhibitor Eradicating Glioblastoma-Initiating Cells

Scientists performed a cell proliferation/death-based drug screening using 10,560 independent compounds. They identified DHODH as a target protein of hit compound 10580 using ligand-fishing and mass spectrometry analysis. The medical efficacy of 10580 was investigated by in vitro cell proliferation/death and differentiation and in vivo tumorigenic assays. [Neuro Oncol] Abstract

Inhibition of Slug Effectively Targets Leukemia Stem Cells via the Slc13a3/Ros Signaling Pathway

Researchers report that Slug promotes leukemogenesis and its loss impaired leukemia stem cell (LSC) self-renewal and delayed leukemia progression. Mechanistically, Slc13a3, a direct target of Slug in LSCs, restricted the self-renewal of LSCs and markedly prolonged recipient survival. [Leukemia] Abstract

USP21 Deubiquitinase Promotes Pancreas Cancer Cell Stemness via Wnt Pathway Activation

Cancer genomic analysis identified frequent amplification of biquitin-specific proteas (USP)21 in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlated with human PDAC progression, and enforced expression of USP21 accelerated murine PDAC tumor growth and drove PanIN to PDAC progression in immortalized human pancreatic ductal cells. [Genes Dev] Abstract | Press Release

Oncogenic Heterogeneous Nuclear Ribonucleoprotein D-Like Modulates the Growth and Imatinib Response of Human Chronic Myeloid Leukemia CD34⁺ Cells via Pre-B-Cell Leukemia Homeobox 1

Heterogeneous nuclear ribonucleoprotein D-like (HNRPDL) modulated imatinib response of K562 cells and HNRPDL silencing sensitized CML CD34⁺ cells to imatinib treatment. Mechanistically, investigators found that the stability of pre-B-cell leukemia homeobox 1 (PBX1) mRNA was sustained by HNRPDL through its binding to a specific motif (ACUAGC) in 3′-untranslated region of PBX1. [Oncogene] Abstract

Loss of TRIM29 Suppresses Cancer Stem Cell-Like Characteristics of PDACs via Accelerating ISG15 Degradation

Scientists demonstrated that correlation expression of TRIM29 and ISG15 in pancreatic ductal adenocarcinomas. They demonstrated that TRIM29 knockdown destabilized ISG15 protein via promoting its processing by calpain 3. [Oncogene] Abstract

Protease Nexin I Is a Feedback Regulator of EGF/PKC/MAPK/EGR1 Signaling in Breast Cancer Cells Metastasis and Stemness

Researchers found that PN-1 was up-regulated in breast cancer, which promoted cell invasion, migration and stemness. Furthermore, by using specific inhibitors, they discovered that epidermal growth factor (EGF) up-regulated PN-1 in breast cancer cells through cascade activation of epidermal growth factor receptor to the activation of protein kinase Cδ, mitogen-activated protein kinase and extracellular signal-related kinase, which finally led to the up-regulation of early growth response protein 1. [Cell Death Dis] Full Article

Lung Tumorspheres Reveal Cancer Stem Cell-Like Properties and a Score with Prognostic Impact in Resected Non-Small-Cell Lung Cancer

Primary cultures from early-stage non-small cell lung cancer patients were established, using sphere-forming assays for CSC enrichment and adherent conditions for the control counterparts. Patient-derived tumorspheres showed self-renewal and unlimited exponential growth potentials, resistance against chemotherapeutic agents, invasion and differentiation capacities in vitro, and superior tumorigenic potential in vivo. [Cell Death Dis] Full Article

Pharmacological mTOR Targeting Enhances the Antineoplastic Effects of Selective PI3Kα Inhibition in Medulloblastoma

Investigators performed studies aimed to enhance the anti-medulloblastoma effects of alpelisib by simultaneous catalytic targeting of the mTOR kinase. Pharmacological mTOR inhibition potently enhanced the suppressive effects of alpelisib on cancer cell proliferation, colony formation and apoptosis and additionally blocked sphere-forming ability of medulloblastoma stem-like cancer cells in vitro. [Sci Rep] Full Article

MicroRNA-29a Inhibits Glioblastoma Stem Cells and Tumor Growth by Regulating the PDGF Pathway

miR-29a expression levels in glioblastoma cells, stem cells and human tumors as well as normal astrocytes and normal brain were measured by quantitative PCR. miR-29a targets were uncovered by target prediction algorithms, and verified by immunoblotting and 3′ UTR reporter assays. [J Neurooncol] Abstract

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Cancer Stem Cells in Prostate Cancer Radioresistance

The authors review the current state of the literature regarding mechanisms of prostate (P)CSC radioresistance, promising PCSC markers and novel PCSC-specific therapeutic approaches and their implications in prostate cancer treatment and prognosis. [Cancer Lett] Abstract

Immunotherapy-Based Targeting and Elimination of Leukemic Stem Cells in AML and CML

Investigators provide an overview of the immunologically relevant molecular targets expressed on leukemic stem cells in patients with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). In addition, they discuss the current status of antibody-based therapies in these malignancies, their mode of action, and successful examples from the field. [Int J Mol Sci] Full Article

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Celyad Successfully Doses First Patient with CYAD-01 Produced with OptimAb Manufacturing Process

Celyad announced the successful administration of CYAD-01 produced with the OptimAb manufacturing process to a patient enrolled in cohort 3 of the Phase I DEPLETHINK trial. [Celyad] Press Release

VBI Vaccines Announces Phase IIa Clinical Evaluation of VBI-1901 Cancer Vaccine Candidate in Combination with GSK’s AS01B Adjuvant System in Recurrent Glioblastoma Patients

VBI Vaccines Inc. announced a collaboration with GlaxoSmithKline (GSK) to clinically evaluate the combination of VBI-1901, VBI’s cancer vaccine immunotherapeutic, with GSK’s proprietary AS01B adjuvant system. [VBI Vaccines Inc.] Press Release

Selvita Announces First Patient Dosed in Phase Ib Study of CDK8 Inhibitor SEL120 in the Treatment of Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome

Selvita announced that the first patient enrolled in the Phase Ib study of company’s selective CDK8 inhibitor, SEL120, has received the first dose. SEL120 is being initially investigated in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. [Selvita] Press Release

Fate Therapeutics Announces FDA Clearance of IND Application for FT596 Off-the-Shelf, iPSC-Derived CAR NK Cell Cancer Immunotherapy

Fate Therapeutics, Inc. announced that the FDA has cleared the company’s Investigational New Drug (IND) application for FT596, the company’s first off-the-shelf chimeric antigen receptor (CAR) natural killer (NK) cell cancer immunotherapy which targets multiple tumor-associated antigens. [Fate Therapeutics, Inc.] Press Release

FDA Confirms Omeros’ Schedule for Rolling Review of the Company’s BLA for Narsoplimab in the Treatment of HSCT-TMA

Omeros Corporation announced that the FDA agreed with the company’s proposed schedule for the rolling review of the Biologics License Application (BLA) for narsoplimab in the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy. [Omeros Corporation] Press Release

EU Research Commissioner Named, but Lacks ‘Research’ in Her Title

Mariya Gabriel, a conservative politician from Bulgaria, is slated to become the next European research chief- although her job title, unlike that of her predecessors, doesn’t include the words “research” or “science.” Some researchers and science policy experts worry the new job title could signal a reduced standing for science within von der Leyen’s proposed executive branch for the European Union, made up of 26 commissioners. [ScienceMagazine] Editorial

US EPA to Eliminate All Mammal Testing by 2035

The US Environmental Protection Agency (EPA) in Washington, DC, announced September 10^th that it will stop conducting or funding studies on mammals by 2035. The move, which is already eliciting strong reactions from groups supporting or opposing experiments on animals, makes EPA the first federal agency to put a hard deadline on phasing out animal research. [Science Magazine] Editorial

NEW Cancer Evolution and Combinatorial Cancer Therapies: Concepts and Challenges
January 19-23, 2020
Banff, Alberta, Canada

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NEW Associate Professor – T-Cell Therapy (Dana-Farber Cancer Institute)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

NEW Postdoctoral Researcher – Stem Cells and Cancer (IRB Barcelona)

Postdoctoral Fellow – Cancer Progression (NIH/NCI – Center for Cancer Research)

Associate Professor – Immunology (Icahn School of Medicine at Mount Sinai)

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

Postdoctoral 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)

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

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