Cancer Stem Cell News Volume 8.10 | Mar 20 2019

TOP STORY

Regulation of the Proline Regulatory Axis and Autophagy Modulates Stemness in TP73/p73 Deficient Cancer Stem-Like Cells

Scientists showed that TP73/p73 deficiency promoted autophagy in cancer stem-like cells by activating the autophagy machinery involving AMPK-TSC-MTOR signaling. Mechanistically, TP73/p73 deficiency-induced autophagy occured as a result of reduced ATP levels resulting from metabolic perturbations within the proline regulatory axis. [Autophagy] Abstract

(Ranked by impact factor of the journal)

CD8⁺ T Cells Expand Stem and Progenitor Cells in Favorable but Not Adverse Risk Acute Myeloid Leukemia

Functionally, CD8⁺ T cells in favorable acute myeloid leukemia (AML) induced the expansion of leukemia stem/progenitor cells (LSPCs) by stimulating the autocrine production of important hematopoietic cytokines such as interleukin-3. In contrast, LSPCs in aggressive AML were characterized by a higher activation of stemness/proliferation-related pathways and developed independent of bone marrow CD8⁺ T cells. [Leukemia] Full Article

Biology and Prognostic Impact of Clonal Plasmacytoid Dendritic Cells in Chronic Myelomonocytic Leukemia

Whole-exome sequencing of sorted monocytes and plasmacytoid dendritic cells (pDCs) identified somatic mutations in genes of the oncogenic RAS pathway in the two cell types of every patient. CD34⁺ cells could generate high amount of pDCs in the absence of FMS-like tyrosine kinase 3-ligand. [Leukemia] Abstract

Wnt and Notch Signaling Govern Self-Renewal and Differentiation in a Subset of Human Glioblastoma Stem Cells

Dual inhibition of Wnt/βcatenin and Notch signaling in glioblastoma stem cells that expressed high levels of the proneural transcription factor ASCL1 led to robust neuronal differentiation and inhibited clonogenic potential. [Genes Dev] Abstract

Modeling Patient-Derived Glioblastoma with Cerebral Organoids

The cerebral organoid glioma model showed that glioma stem cells homed toward the human cerebral organoid and deeply invaded and proliferated within the host tissue, forming tumors that closely phenocopied patient glioblastomas. Furthermore, cerebral organoid tumors formed rapidly and were supported by an interconnected network of tumor microtubes that aided in the invasion of normal host tissue. [Cell Rep] Full Article | Graphical Abstract

PDGFR-Induced Autocrine SDF-1 Signaling in Cancer Cells Promotes Metastasis in Advanced Skin Carcinoma

Scientists showed that CSCs of mouse advanced squamous cell carcinomas (L-CSCs) expressed CXCR4 and CXCR7, both receptors of SDF-1. PDGFRα signaling induced SDF-1 expression and secretion, and the autocrine activation of this pathway in L-CSCs. [Oncogene] Full Article

AKT Drives SOX2 Overexpression and Cancer Cell Stemness in Esophageal Cancer by Protecting SOX2 from UBR5-Mediated Degradation

Investigators showed that in esophageal cancer cell lines, the levels of SOX2 proteins were not directly correlated to the copy numbers of SOX2 genes and were strongly influenced by proteostasis. They showed that AKT was a major determinant for SOX2 overexpression and did so by protecting SOX2 from ubiquitin-dependent protein degradation. [Oncogene] Abstract

IL-8 and CXCR1 Expression Is Associated with Cancer Stem Cell-Like Properties of Clear Cell Renal Cancer

The authors successfully isolated CSCs from established human clear cell renal cell carcinoma cell lines. CSCs displayed high expression of the chemokine IL-8 and its receptor CXCR1. While recombinant IL-8 significantly increased CSC number and properties in vitro, CXCR1 inhibition using an anti-CXCR1 antibody or repertaxin significantly reduced these features. [J Pathol] Abstract

Zika Virus Infection Induces miR34c Expression in Glioblastoma Stem Cells: New Perspectives for Brain Tumor Treatments

Researchers characterized the Zika virus infection mechanism on glioblastoma stem cells, which were considered responsible for the tumor progression and resistance to conventional therapies. Moreover, they explained why the action of this virus was directed to the stem cells in the nervous system counterpart. [Cell Death Dis] Full Article

Long Non-Coding RNA NEAT1 Confers Oncogenic Role in Triple-Negative Breast Cancer through Modulating Chemoresistance and Cancer Stemness

Among 90 long non-coding RNAs, nuclear paraspeckle assembly transcript 1 (NEAT1) was expressed more highly in the blood samples of breast cancer patients than in normal controls. In particular, the expression of NEAT1 was higher in triple-negative breast cancer tissues than other subgroups. [Cell Death Dis] Full Article

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Higher Order Genomic Organization and Epigenetic Control Maintain Cellular Identity and Prevent Breast Cancer

Investigators present a strategic overview of epigenetic regulatory mechanisms including histone modifications and higher order chromatin organization that are perturbed in breast cancer onset and progression. [Genes Chromosomes Cancer] Abstract

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Incysus Therapeutics to Present New Data

Incysus Therapeutics, Inc. announced that Lawrence S. Lamb, PhD, scientific co-founder and Chief Scientific Officer of Incysus will present new preclinical data on Incysus’ drug resistant immunotherapy approach. [Press release from Incysus Therapeutics, Inc. (GlobeNewswire, Inc.) discussing research to be presented at the 2019 American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Pascal Biosciences Partners with Mitacs to Support Innovative Cancer Research at University of British Columbia

Pascal Biosciences Inc. announced a partnership with Mitacs for a multi-year cancer research project at the University of British Columbia (UBC). Mitacs will provide equal funding for research efforts at UBC that will directly support Pascal’s leading cancer development programs. [Pascal Biosciences, Inc.] Press Release

FDA Grants Exemption to Import Alert for Cellectar’s CLR 131 in Pediatric and Adolescent Patients

Cellectar Biosciences, Inc. announced that the FDA has granted an exemption to the import alert placed on the Centre for Probe Development and Commercialization (CPDC) for the use of CLR 131 in connection with the company’s pediatric IND. [Cellectar Biosciences, Inc.] Press Release

EU’s Biggest Research Program Yet Takes Shape

The European Union’s three governing institutions — the Parliament, Council and Commission — reached agreement in the small hours of 20 March on the outline of the EU’s next seven-year research-funding program. [Nature News] Editorial

Canada Budget Overlooks Basic Research

Canada’s 2019 budget, released on 19 March, includes modest increases for Prime Minister Justin Trudeau’s government priorities, including neuroscience and genomics research ― nothing like the historic five-year, Can$4-billion boost for basic science and research unveiled in 2018. [Nature News] Editorial

US Researchers Hope Congress Will Dig NSF Out of a $1 Billion Budget Hole

For the second time in three years, President Donald Trump has recommended deep cuts to the National Science Foundation (NSF) in Alexandria, Virginia. And scientists are hoping Congress will again come to the agency’s rescue. [ScienceInsider] Editorial

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

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

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