Cancer Stem Cell News Volume 6.00 | Jan 4 2017

TOP STORY

Lipid Metabolism Is Potential ‘Achilles’ Heel’ for Cancer Stem Cells

Researchers have discovered a metabolic signature critical for the functioning of “cancer stem cells” that initiate tumor formation. The team also showed how to interfere with this metabolic mechanism in ovarian cancer, inhibiting tumor growth. [Press release from Purdue University discussing online prepublication in Cell Stem Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

CD54–NOTCH1 Axis Controls Tumor Initiation and Cancer Stem Cell Functions in Human Prostate Cancer

Investigators implemented a novel chemoresistant prostate cancer patient-derived xenograft model in NOD/SCID mice and identified CD54 as a candidate gene among the most highly enriched gene expression profiles in prostate tumors exposed to chronic cisplatin administration. [Theranostics] Full Article

RAD51 Mediates Resistance of Cancer Stem Cells to PARP Inhibition in Triple-Negative Breast Cancer

PARP inhibitors have shown promising results in early studies for treatment of breast cancer susceptibility gene (BRCA)–deficient breast cancers; however, resistance ultimately develops. The authors demonstrated that the cancer stem cells in BRCA1-mutant triple-negative breast cancers were resistant to PARP inhibition, and that these cells had both elevated RAD51 protein levels and activity. [Clin Cancer Res] Abstract

Reprogramming Medulloblastoma-Propagating Cells via Combined Antagonism of Sonic Hedgehog and CXCR4

The CXCR4 chemokine and sonic hedgehog (SHH) morphogen pathways are validated therapeutic targets in many cancer types, including medulloblastoma. Researchers showed that dual inhibition of the SHH and CXCR4 pathways exerted potent antitumor effects in a murine model of SHH-subtype medulloblastoma. [Cancer Res] Abstract

Wnt5a Drives an Invasive Phenotype in Human Glioblastoma Stem-Like Cells

Brain invasion by glioblastoma (GBM) determines prognosis, recurrence and lethality in patients, but no master factor coordinating the invasive properties of GBM has been identified. Investigators reported evidence favoring such a role for the non-canonical WNT family member Wnt5a. [Cancer Res] Abstract

REST Represses miR-124 and miR-203 to Regulate Distinct Oncogenic Properties of Glioblastoma Stem Cells

The authors showed that RE1 silencing transcriptional factor (REST) represses 2 major miR gene targets in high-REST-glioblastoma stem-like cells: miR-203, a new target, and miR-124, a known target. They further showed that while miR-124 and the REST-miR-124 pathways regulate self-renewal, apoptosis and invasion, miR-203 and the REST-miR-203 pathways regulate only invasion. [Neuro Oncol] Abstract

CD59 Regulation by SOX2 Is Required for Epithelial Cancer Stem Cells to Evade Complement Surveillance

Using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, scientists found that CD59 was upregulated to protect cancer stem cells (CSCs) from complement-dependent cytotoxicity. Furthermore, they identified that SOX2 upregulates CD59 in epithelial CSCs. [Stem Cell Reports] Full Article

CD133 Confers Cancer Stem-Like Cell Properties by Stabilizing EGFR-AKT Signaling in Hepatocellular Carcinoma

Researchers characterized cancer stem cells (CSCs) in primary hepatocellular carcinoma (HCC) and identified CD133 as a CSC surface marker. CD133⁺ HCC cells displayed more stem cell-like properties, tumor spheroid-forming ability, chemoresistance, migration ability, and tumorigenic capacity than CD133^– HCC cells. [Cancer Lett] Abstract

Bmi1-Positive Cells in the Lingual Epithelium Could Serve as Cancer Stem Cells in Tongue Cancer

The authors recently reported that the polycomb complex protein Bmi1 is a marker for lingual epithelial stem cells, which are involved in the long-term maintenance of lingual epithelial tissue in the physiological state. Using a mouse model of chemically induced tongue cancer and the multicolor lineage tracing method, they found that each unit of the tumor was generated by a single cell and that the assembly of such cells formed a polyclonal tumor. [Sci Rep] Full Article

Sensitizing Leukemia Stem Cells to NF-κB Inhibitor Treatment In Vivo by Inactivation of Both TNF and IL-1 Signaling

Researchers previously reported that autocrine TNF-α (TNF) is responsible for JNK pathway activation in a subset of acute myeloid leukemia (AML) patient samples, providing a survival/proliferation signaling parallel to NF-κB in AML stem cells. In this study, they reported that most TNF-expressing AML cells also express another pro-inflammatory cytokine, IL1β, which acts in a parallel manner. [Oncotarget] Full Article

Targeting Cancer Stem Cell Propagation with Palbociclib, a CDK4/6 Inhibitor: Telomerase Drives Tumor Cell Heterogeneity

Investigators systematically examined the role of telomerase activity in lung and ovarian cancer stem cell propagation. More specifically, they showed that the cancer cells with higher telomerase activity are more energetically activated, with increased mitochondrial mass and function, as well as increased glycolytic activity. [Oncotarget] Full Article

Cathepsin K Cleavage of SDF-1α Inhibits Its Chemotactic Activity towards Glioblastoma Stem-Like Cells

Scientists investigated whether SDF-1α is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on glioma stem-like cells (GSLCs) facilitates their homing to niches. Furthermore, they aimed to prove that SDF-1α cleavage by CatK inactivates SDF-1α and inhibits the invasion of GSLCs. [Biochim Biophys Acta] Abstract

Aldehyde Dehydrogenase Activity Plays No Functional Role in Stem Cell-Like Properties in Anaplastic Thyroid Cancer Cell Lines

The goal of this study was to clarify the functional significance of aldehyde dehydrogenase (ALDH) enzymatic activity on thyroid cancer stem cells properties in anaplastic thyroid cancer cell lines. Investigators found that N,N-diethylaminobenzaldehyde almost completely suppressed ALDH activity without affecting cell proliferation or spherogenicity. In contrast, an ALDH2 inhibitor disulfiram inhibited spherogenicity but did not inhibit ALDH1A3 activity. [Endocrine] Abstract

Isolation, Identification, and Characterization of Cancer Stem Cells: A Review

This review compiles information about different methods of detection and dissociation, side population, cellular markers and establishment culture of cancer stem cells (CSCs), as well as characteristics of CSCs such as tumorigenicity, and signaling pathways associated with self-renewal and the capability of the same histological tumor regeneration in various cancers. [J Cell Physiol] Abstract

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

NewVac Reports Primary Endpoint Met in the Phase II Clinical Trial of Quisinostat in Combination with Paclitaxel and Carboplatin in Platinum-Resistant Ovarian Cancer

NewVac LLC reported meeting all primary endpoints in the Phase II Clinical Trial of quisinostat which NewVac licensed from Janssen Pharmaceutica NV. The clinical trial is evaluating the efficacy and safety of Quisinostat in Platinum-Resistant Ovarian Cancer in combination with Paclitaxel and Carboplatin. [NewVac LLC] Press Release

Tarveda Therapeutics Announces Phase I/IIa Clinical Trial of PEN-221 Underway in Patients with Neuroendocrine Tumors and Small Cell Lung Cancer

Tarveda Therapeutics, Inc. announced that a Phase I/IIa clinical trial evaluating PEN-221 in patients with advanced neuroendocrine tumors and small cell lung cancer expressing the somatostatin receptor 2 is underway, with patients enrolled and treated. [Tarveda Therapeutics, Inc.] Press Release

Lycera Announces Initiation of Phase I/IIa Study ARGON of Immuno-Oncology Candidate LYC-55716 in Patients with Advanced Solid Tumors

Lycera Corp. announced the initiation of a Phase I/IIa clinical trial of the company’s novel immuno-oncology therapeutic candidate LYC-55716, in patients with advanced, relapsed, or refractory solid tumors. [Lycera Corp.] Press Release

US Scientists Fear New Restrictions on Fetal-Tissue Research

House Republicans conclude that tissue from aborted fetuses is of limited value for research and seek to reduce funding. [Nature News] Editorial

Argentina’s Researchers Occupy Science Ministry

Hundreds of young researchers occupied Argentina’s science ministry in Buenos Aires last month, angry at budget cuts that they say have denied them permanent jobs at the country’s National Scientific and Technical Research Council. The occupation was the most extreme action yet by Argentinian scientists after months of protests at last year’s budget, the first under President Mauricio Macri. And the occupation seems to have paid off, in part: many of those involved have been offered extensions to their fellowships. [Nature News] Editorial

NEW Keystone Symposium: Tumor Metabolism: Mechanisms and Targets
March 5-9, 2017
Whistler, Canada

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

NEW Postdoctoral Research – Cancer Genetics and Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Brain Cancer Stem Cells (University of Alabama at Birmingham)

Tenure Track Faculty – Stem Cells and Regenerative Medicine (University of Notre Dame)

Postgraduate Research Associate – Organic/Medicinal Chemistry (University of Oxford)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Assistant Professor – Cancer Research (National University of Singapore)

Postdoctoral Fellow – Cancer Research (National University of Singapore)

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

Postdoctoral Fellow – Viruses & Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Liver Cancer and Developmental Biology (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cancer Genetics/Epigenetics (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Cell Cycle Control and Tumorigenesis (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Ubiquitin System and Cancer (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Tumor Immunology (Moffitt Cancer Center)

Tier 2 Canada Research Chair – Pharmacology (University of Ottawa)

Assistant Professor – Cancer Biology, Cancer Genomics and Precision Medicine (Wake Forest Baptist Comprehensive Cancer Center)

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