Cancer Stem Cell News Volume 8.13 | Apr 10 2019

TOP STORY

A Multiscale Map of the Stem Cell State in Pancreatic Adenocarcinoma

Researchers used RNA sequencing (seq), chromatin immunoprecipitation-seq, and genome-wide CRISPR analysis to map the molecular dependencies of pancreatic cancer stem cells, highly therapy-resistant cells that preferentially drove tumorigenesis and progression. This integrated genomic approach revealed an unexpected utilization of immuno-regulatory signals by pancreatic cancer epithelial cells. [Cell] Abstract | Press Release | Graphical Abstract

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USP9X Deubiquitinates ALDH1A3 and Maintains Mesenchymal Identity in Glioblastoma Stem Cells

Scientists identified ubiquitin-specific protease 9X (USP9X) as a bona fide deubiquitinase of aldehyde dehydrogenase 1A3 (ALDH1A3) in mesenchymal (MES) glioblastoma stem cells (GSCs). USP9X interacted with, depolyubiquitylated, and stabilized ALDH1A3. Moreover, they showed that FACS-sorted USP9X^hi cells were enriched for MES GSCs with high ALDH1A3 activity and potent tumorigenic capacity. [J Clin Invest] Full Article

A Positive Feedback Loop between Cancer Stem-Like Cells and Tumor- Associated Neutrophils Controls Hepatocellular Carcinoma Progression

Investigators showed that tumor-associated neutrophils secreted BMP2 and TGF-β2, and triggered miR-301b-3p expression in hepatocellular carcinoma (HCC) cells, subsequently suppressed gene expression of limbic system-associated membrane protein and CYLD lysine 63 deubiquitinase and increased stem cell characteristics in HCC cells. [Hepatology] Abstract

Identification of a Leukemia-Initiating Stem Cell in Human Mast Cell Leukemia

The authors described that leukemic stem cells in mast cell leukemia (MCL) resided within a CD34⁺/CD38^– fraction of the clone. Whereas highly purified CD34⁺/CD38^– cells engrafted NSG_hSCF mice with fully manifesting MCL, no MCL was produced by CD34⁺/CD38⁺ progenitors or the bulk of KIT⁺/CD34^– mast cells. [Leukemia] Full Article

Oncogenic PIK3CA Promotes Cellular Stemness in an Allele Dose-Dependent Manner

While heterozygous induced pluripotent stem cells remained largely similar to wild-type cells, homozygosity for PIK3CA^H1047R caused widespread, cancer-like transcriptional remodeling, partial loss of epithelial morphology, up-regulation of stemness markers, and impaired differentiation to all three germ layers in vitro and in vivo. [Proc Natl Acad Sci USA] Full Article

REST-DRD2 Mechanism Impacts Glioblastoma Stem Cell-Mediated Tumorigenesis

Researchers examined two independent high repressor element-1 silencing transcription factor (REST) glioblastoma stem cell (GSC) lines using genome-wide assays, biochemical validations, gene knockdown analysis, and mouse tumor models. Genome-wide transcriptome and DNA-binding analyses suggested the dopamine receptor D2 (DRD2) gene, a dominant regulator of neurotransmitter signaling, as a direct target of REST. [Neuro Oncol] Abstract

Pathogenic Mutations in Neurofibromin Identifies a Leucine-Rich Domain Regulating Glioma Cell Invasiveness

Scientists reported that the leucine-rich domain (LRD) of neurofibromin inhibited invasion of human glioblastoma cells without affecting their proliferation. Moreover, under conditions tested, the NF1-LRD failed to hydrolyze Ras-GTP to Ras-GDP, suggesting that its suppressive function was independent of Ras signaling. [Oncogene] Full Article

Prosaposin Is a Biomarker of Mesenchymal Glioblastoma and Regulates Mesenchymal Transition through the TGF-β1/Smad Signaling Pathway

The human glioma cell lines and patient derived glioma stem cells were studied in vitro and in vivo, revealing that mesenchymal glioblastoma (GBM) expressed and secreted the highest level of prosaposin (PSAP) among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial-mesenchymal transition-like processes in vivo and in vitro. [J Pathol] Abstract

Lipolytic Inhibitor G0S2 Modulates Glioma Stem-Like Cell Radiation Response

Using genetic approaches targeting G0/G1 switch gene 2 (G0S2) in glioma cells and glioma stem-like cells (GSCs), investigators found that knockdown of G0S2 promoted lipid droplet turnover, inhibited GSC radioresistance, and extended survival of xenograft tumor mice with or without ionizing radiation. In contrast, overexpression of G0S2 promoted glioma cell radiation resistance. [J Exp Clin Cancer Res] Full Article

Mild Thermotherapy and Hyperbaric Oxygen Enhance Sensitivity of TMZ/PSi Nanoparticles via Decreasing the Stemness in Glioma

Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), were combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, the authors detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO. [J Nanobiotechnology] Full Article

High Skp2 Expression Is Associated with a Mesenchymal Phenotype and Increased Tumorigenic Potential of Prostate Cancer Cells

Increased Skp2 expression was observed in prostate cancer cell lines with mesenchymal and CSC-like phenotype compared to their epithelial counterparts. Conversely, the CSC-like phenotype was diminished in cells in which SKP2 expression was silenced. Furthermore, investigators observed that Skp2 downregulation led to the decrease in subpopulation of CD44⁺CD24^– cancer stem-like cells. [Sci Rep] Full Article

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The Role of SVZ Stem Cells in Glioblastoma

The authors summarize current findings about links between neural stem cells and cancer stem cells in glioblastoma and discuss current therapeutic approaches, which arise as a result of identifying the cell of origin in glioblastoma. [Cancers] Full Article

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Moleculin Announces Successful Expansion of Its Leukemia Drug Program

Moleculin Biotech, Inc. announced it has successfully expanded the clinical supply of Annamycin for its on-going clinical trials via BSP Pharmaceuticals S.p.A. in Latina, Italy. [Moleculin Biotech, Inc.] Press Release

Daiichi Sankyo Provides Update on Ongoing FDA Review for Quizartinib for Treatment of Patients with Relapsed/Refractory FLT3-ITD AML

Daiichi Sankyo Company, Limited announced that the FDA has extended the review period for the New Drug Application of quizartinib, an investigational FLT3 inhibitor, currently under priority review for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML). [Daiichi Sankyo Company, Ltd] Press Release

Racism Rife at Top South African University, Says Report

A damning report that says racism is entrenched at the University of Cape Town has reignited discussions about how to erase the divisive legacy of colonialism at South Africa’s top research institutions. [Nature News] Editorial

FDA, New York Attorney General Go After Stem Cell Clinics

On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [The Scientist] Editorial

NEW Keystone Symposia: Tumor Metabolism
March 8-12, 2020
Banff, Alberta, Canada

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

Postdoctoral Fellowship – Cancer and Glioma Stem Cell Biology (Cornell University)

Research Fellow – Developmental Biology & Cancer (University College London)

Postdoctoral Fellow – Glioblastoma Multiforme Research (Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellowship – Hematopoietic Stem Cells (Washington University in St. Louis)

Assistant, Associate, or Full Professor – Breast Cancer (University Hospitals Cleveland Medical Center)

Postdoctoral Associate – 3D Epigenetic Landscape at Single Cell Level (Sanford Burnham Prebys Medical Discovery Institute)

Postdoctoral & Research Associate Positions – Cancer, Cancer Stem Cells, Normal Development, and Aging (Johns Hopkins University)

Faculty Position – Prostate Cancer Biology and Cancer Epigenetics (Northwestern University Feinberg School of Medicine)

Tenure Track Faculty Position – Cancer Biology & Therapeutics (Geisel School of Medicine at Dartmouth)

Postdoctoral Position – Ovarian Cancer Stem Cells (University of Minnesota)

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