Cancer Stem Cell News Volume 6.29 | Jul 26 2017

TOP STORY

Targeting NEK2 Attenuates Glioblastoma Growth and Radioresistance by Destabilizing Histone Methyltransferase EZH2

Investigators identified NIMA-related kinase 2 (NEK2) as a functional binding protein of enhancer of zeste homolog 2 (EZH2) that plays a critical role in the posttranslational regulation of EZH2 protein in glioma stem cells (GSCs). NEK2 was among the most differentially expressed kinase-encoding genes in GSC-containing cultures, and it was required for in vitro clonogenicity, in vivo tumor propagation, and radioresistance. [J Clin Invest] Full Article

(Ranked by impact factor of the journal)

MYC-Regulated Mevalonate Metabolism Maintains Brain Tumor Initiating Cells

The authors link metabolic dysregulation in patient-derived brain tumor initiating cells (BTICs) to a nexus between MYC and mevalonate signaling, which could be inhibited by statin or 6-fluoromevalonate treatment. BTICs preferentially expressed mevalonate pathway enzymes, which they found regulated by novel MYC binding sites, validating an additional transcriptional activation role of MYC in cancer metabolism. [Cancer Res] Abstract

NFATc2 Enhances Tumor-Initiating Phenotypes through the NFATc2/SOX2/ALDH Axis in Lung Adenocarcinoma

Scientists showed the calcium pathway transcription factor NFATc2 is a novel regulator of lung tumor initiating cells (TIC) phenotypes, including tumorspheres, cell motility, tumorigenesis, as well as in vitro and in vivo responses to chemotherapy and targeted therapy. In human lung cancers, high NFATc2 expression predicted poor tumor differentiation, adverse recurrence-free and cancer-specific overall survivals. [eLife] Full Article

Wilms Tumor NCAM-Expressing Cancer Stem Cells as Potential Therapeutic Target for Polymeric Nanomedicine

Researchers examined the ability of the conjugate to inhibit Wilms tumor by targeting the neural cell adhesion molecule-expressing CSCs. Results showed that the conjugate selectively depleted the CSC population of the tumors and effectively inhibited tumor growth without causing toxicity. [Mol Cancer Ther] Abstract

Detailed Longitudinal Sampling of Glioma Stem Cells In Situ Reveals Chr7 Gain and Chr10 Loss As Repeated Events in Primary Tumor Formation and Recurrence

The authors developed an extensive dataset for a GBM case via the generation of polyclonal and monoclonal glioma stem cell lines from initial diagnosis, as well as from multiple sections of distant tumor locations of the deceased patient’s brain following tumor recurrence. Their analyses revealed the tissue-wide expansion of a new clone in the recurrent tumor as well as chromosome 7 gain and chromosome 10 loss as repeated genomic events in primary and recurrent disease. [Int J Cancer] Abstract

Autophagy Inhibition Reduces Chemoresistance and Tumorigenic Potential of Human Ovarian Cancer Stem Cells

Scientists investigated both in vitro and in vivo the autophagic activity and the effects of the perturbation of this pathway in CSCs isolated from epithelial ovarian cancer ascitic effusions. Ovarian CSCs, identified according to their CD44/CD117 co-expression, presented a higher basal autophagy compared with the non-stem counterpart. [Cell Death Dis] Full Article

Glioblastoma and Glioblastoma Stem Cells Are Dependent on Functional MTH1

Researchers found MTH1 expression levels elevated and correlated with glioblastoma multiforme (GBM) aggressiveness and discovered that siRNA knock-down or inhibition of MTH1 with small molecules efficiently reduced viability of patient-derived GBM cultures. The effect of MTH1 loss on GBM viability was likely mediated through incorporation of oxidized nucleotides and subsequent DNA damage. They revealed that MTH1 inhibition targets GBM independent of aggressiveness as well as potently kills putative GBM stem cells in vitro. [Oncotarget] Full Article

Gynura divaricata Attenuates Tumor Growth and Tumor Relapse after Cisplatin Therapy in HCC Xenograft Model through Suppression of Cancer Stem Cell Growth and Wnt/β-Catenin Signaling

Researchers evaluated the anti-cancer and cancer stabilization effect of water extract of the aerial part of G. divaricata (GD extract) both in vitro and in vivo. GD extract inhibited cancer sphere formation and reduced the expression of CSC markers. GD extract suppressed Huh7 tumor growth, Ki-67 expression and prolonged the anti-liver cancer effect of cisplatin in vivo. [J Ethnopharmacol] Abstract | Graphical Abstract

Pleomorphism and Drug Resistant Cancer Stem Cells Are Characteristic of Aggressive Primary Meningioma Cell Lines

Meningioma tissues and primary cell lines were investigated using whole transcriptome microarray analysis, immunofluorescence staining of CSCs markers, and drug treatment with cisplatin or etoposide. Unsupervised hierarchical clustering of six meningioma samples separated tissues into two groups. Analysis identified stem cells related pathways to be differential between the two groups and indicated the deregulation of the stem cell associated genes Reelin, Calbindin 1 and Anterior Gradient 2 Homolog. [Cancer Cell Int] Full Article

Hybrid Nanoparticles Coated with Hyaluronic Acid Lipoid for Targeted Co-Delivery of Paclitaxel and Curcumin to Synergistically Eliminate Breast Cancer Stem Cells

The authors fabricated a breast cancer stem cell (bCSC)-targeting co-delivery system by attaching a lipoid (HA-HDA) to the surface of hydrophobic PLGA nanoparticles to co-deliver the widely used chemotherapy agent PTX and the selective inhibitor of CSCs curcumin. This co-delivery system was capable of targeting bCSCs via an interaction between HA and the CD44 receptor on the membrane of bCSCs, and it could efficiently eliminated the bCSC population, decreased the mammosphere formation of bCSCs, and inhibited the migration of bCSCs. [J Mater Chem B] Abstract

Advances in Cancer Stem Cell Targeting: How to Strike the Evil at Its Root

The authors report on targeted therapies gearing towards the CSC’s internal and membrane-anchored markers using agents such as antibody derivatives, nucleic therapeutics, small molecules and genetic payloads. They summarize recent progress and remaining challenges in therapeutic strategies to combat CSCs. [Adv Drug Deliv Rev] Abstract | Graphical Abstract

Vascular Regulation of Glioma Stem-Like Cells: A Balancing Act

Scientists review recent findings, focusing on the mechanisms that underlie glioma stem-like cell (GSC)/vascular communication. They further discuss how plasticity enables GSCs to respond to vascular changes by interconverting bidirectionally between states, and address the therapeutic implications of this dynamic response. [Curr Opin Neurobiol] Full Article

Visit our reviews page to see a complete list of reviews in the cancer stem cell research field.

CIRM Approves $5.8 Million Grant for CAR-T Therapy that Targets Cancer Stem Cells

The Independent Citizens Oversight Committee of the California Institute for Regenerative Medicine (CIRM) today unanimously approved a $5.8 million award to University of California San Diego School of Medicine researchers to develop a new immunotherapy in which patients’ cells would be equipped with a special receptor that recognizes and targets cancer stem cells, whose survival abilities often render standard therapies ineffective or short-term. [University of California, San Diego] Press Release

Jeffrey and Marieke Rothschild Gift Establishes Stanford Center for Cancer Cell Therapy

The Stanford Cancer Institute has received a $10 million gift from Silicon Valley entrepreneur Jeffrey Rothschild and his wife, Marieke, to advance research in cancer cell therapy, which is considered the vanguard of cancer treatment today. The gift launches the Stanford Center for Cancer Cell Therapy, which will support research and clinical trials of treatments that use the power of the patients’ own immune system to attack and kill tumor cells. [Stanford Medicine] Press Release

Budding UK Innovation Agency Gains Cash — and Clout

UK scientists fearful for their research funds ahead of Brexit were cheered when the government announced it would plough an extra £4.7 billion (US$6.1 billion) into research and development by 2020–21. But the biggest winner from the largely industry-focused cash may be a government innovation agency that is rapidly gaining clout. [Nature News] Editorial

Ding, Ding, Ding! CRISPR Patent Fight Enters Next Round

The University of California has fired another legal salvo in the prolonged patent battle over CRISPR, the revolutionary gene-editing technology that has spawned a billion dollar industry. [ScienceInsider] Editorial

Senate Spending Panel Would Squeeze Science Agencies but Exceed Trump Request

A Senate spending panel voted today to reduce funding in 2018 below current levels for several science agencies under its jurisdiction. [ScienceInsider] Editorial

NEW 11^th American Association for Cancer Research (AACR)-Japanese Cancer Association (JCA) Joint Conference
February 8-12, 2019
Maui, Hawaii, United States

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

NEW Postdoctoral Fellow – Tumor Microenvironment and Cancer Stem Cells (Duke University Medical Center)

Postdoctoral Research Fellow – Immunology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cell Signaling and Cancer Biology (Rutgers Cancer Institute of New Jersey)

Postdoctoral Fellowship – Epithelial Stem Cell Biology (University of Michigan Healthcare System)

Postdoctoral, PhD and Technician Positions – Cancer Metabolism (Université Catholique de Louvain)

Research Scientist – Bioinformatics (University of Glasgow)

Postdoctoral Position – Cancer Biology (UCLA)

Postdoctoral Scholar – Cancer Research (UCLA G.O. Discovery Laboratory)

Faculty Positions – Cancer and Stem Cell Biology (Sun Yat-Sen University)

Postdoctoral Fellows – Cancer Stem Cell Biology (Genome Institute of Singapore)

Research Officers – Cancer Stem Cell Biology (Genome Institute of Singapore)

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