Cancer Stem Cell News Volume 5.45 | Nov 16 2016

TOP STORY

Qki Deficiency Maintains Stemness of Glioma Stem Cells in Suboptimal Environment by Downregulating Endolysosomal Degradation

Postnatal co-deletion of Pten and Trp53 in mouse neural stem cells (NSCs) leads to the expansion of these cells in their subventricular zone (SVZ) niches but fails to maintain stemness outside the SVZ. Researchers discovered that Qki is a major regulator of NSC stemness. [Nat Genet] Abstract | Press Release

(Ranked by impact factor of the journal)

WIP Drives Tumor Progression through YAP/TAZ-Dependent Autonomous Cell Growth

The authors showed that high levels of the actin cytoskeleton-associated protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are linked to the tumor-initiating cell phenotype. They found that WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system. [Cell Rep] Full Article | Graphical Abstract

Rapidly Cycling Lgr5⁺ Stem Cells Are Exquisitely Sensitive to Extrinsic Dietary Factors that Modulate Colon Cancer Risk

Investigators examined the effect of n-3 polyunsaturated fatty acids (PUFAs) and polyphenol (curcumin) combination on leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5⁺) stem cells during tumor initiation and progression in the colon compared with an n-6 PUFA-enriched control diet. [Cell Death Dis] Full Article

ERK/Drp1-Dependent Mitochondrial Fission Is Involved in the MSC-Induced Drug Resistance of T-Cell Acute Lymphoblastic Leukemia Cells

The authors tested both indirect (Transwell) and direct coculture strategies, and found that mesenchymal stem cells (MSCs) protected T-cell acute lymphoblastic leukemia cells from chemotherapeutic cell death and cytotoxicity under both culture conditions. In addition, cell viability was higher in the direct contact system compared with the Transwell system. [Cell Death Dis] Full Article

Protein Tyrosine Phosphatase PTPN3 Promotes Drug Resistance and Stem Cell-Like Characteristics in Ovarian Cancer

Scientists found that protein tyrosine phosphatase PTPN3 gene expression was substantially increased in both cisplatin and doxorubicin-resistant ovarian cancer cells. Silencing of PTPN3 restored sensitivity to cisplatin and doxorubicin in resistant ovarian cancer cells. [Sci Rep] Full Article

TRIM28 Multi-Domain Protein Regulates Cancer Stem Cell Population in Breast Tumor Development

Investigators evaluated the role of Tripartite motif-containing protein 28 (TRIM28)/Krüppel-associated box (KRAB)-associated protein 1 (KAP1) protein in the regulation of breast cancer stem cells (CSC) populations and tumorigenesis in vitro and in vivo. Downregulation of TRIM28 expression in xenografts led to deceased expression of pluripotency and mesenchymal markers, as well as inhibition of signaling pathways involved in the complex mechanism of CSC maintenance. [Oncotarget] Full Article

Microenvironmental Networks Promote Tumor Heterogeneity and Enrich for Metastatic Cancer Stem-Like Cells in Luminal-A Breast Tumor Cells

The authors exposed Luminal-A breast cancer cells in culture to combine “tumor microenvironment (TME) stimulation”, representing three typical arms of the breast TME: hormonal, inflammatory and growth-promoting. In addition to enriching the tumor cell population with CD44⁺/β1⁺ cells, TME stimulation selected for CD44⁺/CD24^low/- stem-like cells, that were further enriched by doxorubicin treatment and demonstrated high plasticity in vitro and in vivo. [Oncotarget] Full Article

miR-589-5p Inhibits MAP3K8 and Suppresses CD90⁺ Cancer Stem Cells in Hepatocellular Carcinoma

miR-589-5p and miR-33b-5p were down-regulated in CD90⁺ cells. Overexpression of miR-589-5p suppressed CD90⁺ cancer stem cells (CSC) characteristics such as Oct4, Sox2 and Nanog expression, a high likelihood of forming cell spheres, high invasiveness and high tumorigenicity. [J Exp Clin Cancer Res] Full Article

Let-7 Inhibits Self-Renewal of Hepatocellular Cancer Stem-Like Cells through Regulating the Epithelial-Mesenchymal Transition and the Wnt Signaling Pathway

Let-7a effectively repressed cell proliferation and viability, and in stem-like cells, also let-7a decreased the efficiency of sphere formation in stem-like cells. The suppression of epithelial-mesenchymal transition signaling factors in human hepatocellular carcinoma cells contributed to let-7’s induced tumor viability repression and Wnt activation repression. [BMC Cancer] Full Article

GINS2 Regulates Matrix Metallopeptidase 9 Expression and Cancer Stem Cell Property in Human Triple Negative Breast Cancer

Researchers investigated the possible effect and particular mechanism of GINS in breast cancer cells. They showed that expression of GINS2 is enriched in triple negative breast cancer (TNBC) cell lines. Furthermore, GINS2 knockdown decreased the growth, invasive ability and stem-like property of TNBC cells. [Biomed Pharmacother] Abstract

Cell of Origin of Glioma: Biological and Clinical Implications

Diverse distinct cell populations in the adult brain have been reported to give rise to gliomas, although how these studies relate physiologically to mechanisms of spontaneous tumor formation via accumulation of tumor-initiating mutations within a single cell are less well developed. Recent studies in animal models indicate that the lineage of the tumor-initiating cell may contribute to the biological and genomic phenotype of glioblastoma. [Br J Cancer] Full Article

Eradicating Quiescent Tumor Cells by Targeting Mitochondrial Bioenergetics

The presence of quiescent cell populations in solid tumors represents a major challenge for disease eradication. Such cells are generally present in poorly vascularized tumor areas, show limited sensitivity to traditional chemotherapeutical drugs, and tend to resume proliferation, resulting in tumor reseeding and growth. There is growing recognition of the importance of developing therapies that target these quiescent cell populations to achieve long-lasting remission. [Trends Cancer] Abstract

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Blueprint Medicines to Present Preliminary Data from Ongoing Phase I Clinical Trials for BLU-285 and BLU-554

Blueprint Medicines Corporation announced that preliminary data from the Phase I clinical trials evaluating BLU-285 for the treatment of advanced gastrointestinal stromal tumors and BLU-554 for the treatment of advanced hepatocellular carcinoma will be presented. [Press release from Blueprint Medicines Corporation discussing research to be presented at 28^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, Munich] Press Release

Boehringer Ingelheim Bevacizumab Biosimilar Candidate Demonstrates Bioequivalence to Avastin^®

Boehringer Ingelheim announced new data from the Phase I INVICTAN^®-1 study, which show that BI 695502, its bevacizumab biosimilar candidate, is bioequivalent to U.S.-licensed and EU-approved Avastin^®. Avastin^® is an angiogenesis inhibitor that is used to treat a variety of cancers. [Boehringer Ingelheim GmbH] Press Release

Boston Biomedical Announces Orphan Drug Designation for Napabucasin in Pancreatic Cancer

Boston Biomedical announced that its lead investigational compound, napabucasin, has received Orphan Drug Designation from the U.S. Food and Drug Administration in the treatment of pancreatic cancer. This is the second Orphan Drug Designation for napabucasin, an orally administered agent designed to inhibit cancer stemness pathways by targeting STAT3; the first designation was for gastric cancer including gastroesophageal junction cancer. [Boston Biomedical] Press Release

Opdivo (Nivolumab) and Yervoy (Ipilimumab) Regimen Shows Promising Efficacy and Safety in Previously Treated Patients with Advanced Form of Bladder Cancer

Bristol-Myers Squibb Company announced additional results from the Phase I/II open-label CheckMate-032 trial investigating two combination schedules of Opdivo plus Yervoy in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy. In these preliminary data, the primary endpoint of investigator-assessed confirmed objective response rate in patients who received Opdivo 1 mg/kg plus Yervoy 3 mg/kg compared to 26.0% in patients treated with Opdivo 3 mg/kg plus Yervoy 1 mg/kg. [Bristol-Myers Squibb Company] Press Release

Interim Phase I/II Data Show Encouraging Clinical Benefit for Lirilumab in Combination with Opdivo (Nivolumab) in Patients with Advanced Platinum Refractory Squamous Cell Carcinoma of the Head and Neck

Bristol-Myers Squibb Company and Innate Pharma SA announced an interim efficacy analysis from a Phase I/II study of the combination of lirilumab and Opdivo in the cohort of advanced platinum refractory squamous cell carcinoma of the head and neck, including exploratory biomarker analyses of patient response by level of PD-L1 expression. [Bristol-Myers Squibb Company] Press Release

CRISPR Gene-Editing Tested in a Person for the First Time

A Chinese group has become the first to inject a person with cells that contain genes edited using the revolutionary CRISPR–Cas9 technique. [Nature News] Editorial

Disgraced Stem-Cell Entrepreneur Under Fresh Investigation

Public prosecutors in Turin, Italy, are investigating whether disgraced stem-cell entrepreneur Davide Vannoni — convicted on criminal charges last year for administering unproven stem-cell therapies in Italy — is offering his treatments again, this time in eastern Europe. [Nature News] Editorial

The Ultimate Experiment: How Trump Will Handle Science

The long campaign for the White House is over — but incoming US president Donald Trump’s work is just starting. With just two months before his inauguration on 20 January, he and his staff are busy vetting candidates for top government jobs and clarifying the agenda for his first few months in office. [Nature News] Editorial

Embryonic Stem Cells and Fetal Tissue Research—Will Trump Intervene?

Of all the materials valued in biomedical research, embryonic stem (ES) cells and fetal tissue have gotten disproportionate attention from politicians. Because creating ES cell lines initially requires destroying a human embryo, President George W. Bush tightly restricted the use of federal funds for research on all but a few stem cell lines. President Barack Obama then made lifting those restrictions one of his first official actions after he took office in 2009. [Science Insider] Editorial

NEW ANOTHER DEATH in the ALPS: Cell Death, Inflammation and Cancer
January 10-14, 2017
Obergurgl, Austria

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NEW Postdoctoral Fellow – Statistical Computing in Cancer Research and Personalized Medicine (European Molecular Biology Laboratory)

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

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

Postdoctoral Position – Physical Oncology (Houston Methodist Research Institute)

Assistant, Associate or Full Professor – Cancer Biology (University of Pennsylvania)

Research Scientist – Epigenetic Mechanisms Involving Histone Deacetylases, Methyltransferases and Demethylases (The University of Texas MD Anderson Cancer Center)

Associate Professor – Experimental Radiation Oncology (The University of Texas MD Anderson Cancer Center)

Assistant Professor (Tenure Track) – Mechanisms Related to Aging, Cancer and Stem Cell Biology)

Scientific Developer – Computational Systems Biology of Cancer (Institut Curie)

Post-Doctoral Researcher – Influential Nodes and Links in Multi-Level Cancer-Related Networks (Luxembourg Institute of Health)

Two Assistant Professor Positions – Molecular Medicine (University of Georgia)

Postdoctoral Associate – Glioma Stem Cell Biology and Cerebral Organoid (Weill Cornell Medicine)

Postdoctoral Position – Metastatic Breast Cancer (Purdue Center for Cancer Research)

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