Cancer Stem Cell News Volume 6.13 | Apr 5 2017

TOP STORY

Noncanonical GLI1 Signaling Promotes Stemness Features and In Vivo Growth in Lung Adenocarcinoma

Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. Scientists showed that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. [Oncogene] Full Article

(Ranked by impact factor of the journal)

Stearoyl-CoA-Desaturase 1 Regulates Lung Cancer Stemness via Stabilization and Nuclear Localization of YAP/TAZ

The authors showed, using primary cell cultures from human lung adenocarcinoma, that the effectors of the Hippo pathway, Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are required for the generation of lung cancer three-dimensional cultures and that stearoyl-CoA-desaturase 1 knock down and pharmacological inhibition both decrease expression, nuclear localization and transcriptional activity of YAP and TAZ. [Oncogene] Abstract

The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

Researchers analyzed the genomic landscape of circulating tumor cells (CTCs) from 29 multiple myeloma (MM) patients, including eight cases with matched/paired bone marrow (BM) tumor cells. Their results showed that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. [Cell Rep] Full Article | Graphical Abstract

HDAC4 and HDAC6 Sustain DNA Double Strand Break Repair and Stem-Like Phenotype by Promoting Radioresistance in Glioblastoma Cells

The role of histone deacetylase (HDAC)4 and 6 in glioblastoma (GBM) radioresistance was investigated. Scientists found that tumor samples from 31 GBM patients, who underwent temozolomide and radiotherapy combined treatment, showed HDAC4 and HDAC6 expression in 93.5% and 96.7% of cases, respectively. They also showed that p53^WT expression contributed to the radiotherapy lethal effects and that HDAC4 or HDAC6 sustained GBM stem-like radioresistant phenotype. [Cancer Lett] Abstract

Hypoxia-Mediated Epigenetic Regulation of Stemness in Brain Tumor Cells

Activation of pluripotency regulatory circuit is an important event in solid tumor progression and the hypoxic microenvironment is known to enhance the stemness feature of some cells. The authors demonstrated the role of hypoxia-mediated epigenetic modifications in regulating expression of core pluripotency factors, OCT4 and NANOG, in glioma cells. [Stem Cells] Abstract

Highly-Sensitive Capture of Circulating Tumor Cells Using Micro-Ellipse Filters

Circulating tumor cells detection, enumeration and characterization with microfluidic chips has critical significance in cancer prognosis offering a non-invasive “liquid biopsy”. Based on physical differences of size and deformability, scientists explored micro-ellipse filters consisting of microfuidic slits in series gradually narrowed. [Sci Rep] Full Article

Chitosan Promotes Cancer Progression and Stem Cell Properties in Association with Wnt Signaling in Colon and Hepatocellular Carcinoma Cells

Investigators grew colon and hepatocellular carcinoma cells on chitosan membranes and evaluated the tumor progression and the cancer stem cell (CSC) properties. Experimental results showed that culturing cancer cells on chitosan increased cell motility, drug resistance, quiescent population, self-renewal capacity, and the expression levels of stemness and CSC marker genes, such as OCT4, NANOG, CD133, CD44, and EpCAM. [Sci Rep] Full Article

Synergistic Targeting of Breast Cancer Stem-Like Cells by Human γδ T Cells and CD8⁺ T Cells

To help develop novel immunotherapy approaches that efficiently target cancer stem cells (CSCs), an experimental model allowing reliable distinction of CSCs and non-CSCs was set up to study their interaction with non-MHC restricted γδ T cells and antigen-specific CD8⁺ T cells. The findings identify a powerful synergism between MHC-restricted and non-MHC restricted T cells in the eradication of cancer cells including breast CSCs. [Immunol Cell Biol] Full Article

Bax Activation Blocks Self-Renewal and Induces Apoptosis of Human Glioblastoma Stem Cells

A derivative of BAM-7, named BTC-8, was employed to explore the effects of Bax activation in different human glioblastoma (GBM) cells and in their stem cell subpopulation. BTC-8 inhibited GBM cell proliferation, arrested cell-cycle and induced apoptosis through the induction of mitochondrial membrane permeabilization. [ACS Chem Neurosci] Abstract

MiR-223/PAX6 Axis Regulates Glioblastoma Stem Cell Proliferation and the Chemo Resistance to TMZ via Regulating PI3K/Akt Pathway

Researchers aimed to determine whether inhibition of the miR-223/paired box 6 (PAX6) pathway could increase the sensitivity of glioma to temozolomide (TMZ). An elevated level of miR-223 was observed in glioma tissues. Exogenous miR-223 promoted cell survival when exposed to TMZ, while miR-223 inhibition could reverse this process. [J Cell Biochem] Abstract

Apoptosis and Cell Cycle Regulatory Effects of Adenosine by Modulation of GLI-1 and ERK1/2 Pathways in CD44⁺ and CD24⁻ Breast Cancer Stem Cells

Investigators designed a study to evaluate the effect of adenosine and its signaling pathways in breast cancer stem cells (CSCs). Adenosine reduced CSCs population and mammosphere formation in breast CSCs. Adenosine induced G1 cell cycle arrest in breast CSCs in conjunction with a marked down-regulation of cyclin D1 and CDK4. [Cell Prolif] Abstract

Cancer Stem Cells with Increased Metastatic Potential as a Therapeutic Target for Esophageal Cancer

The authors review the current literature on esophageal cancer stem cells (CSCs) and related metastases. Esophageal CSC markers are discussed followed by the pathways that initiate and sustain these cells. [Semin Cancer Biol] Full Article

Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications

Scientists discuss progress in cancer stem cell biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. [Neurotherapeutics] Abstract

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

Siamab Therapeutics Presents New Preclinical Data for Its Novel Anti-STn Antibodies, Antibody-Drug Conjugates, and Anti-STn Bispecific Antibodies

Siamab Therapeutics, Inc. announced the presentation of two posters featuring new preclinical data for its novel anti-Sialyl-Tn (STn) antibodies, antibody-drug conjugates, and anti-STn, anti-CD3 bispecific antibodies. [Press release from Siamab Therapeutics, Inc. (Business Wire, Inc.) discussing research presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release | Abstract 1 | Abstract 2

Boston Biomedical Presents New Preclinical Data Highlighting the Potential Role of Cancer Stemness Inhibition

Boston Biomedical presented preclinical data from its research and development portfolio. Data from the preclinical study evaluated napabucasin in combination with an anti-PD-1 antibody, an immune checkpoint inhibitor, and found that the combination was able to sensitize mice with colorectal cancer to checkpoint inhibitors. [Press release from Boston Biomedical discussing research presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release

Eleven Biotherapeutics Presents New Preclinical Data Supporting the Potential of the Company’s Locally- and Systematically-Administered Drug Candidates

Eleven Biotherapeutics, Inc. announced new preclinical data with VB4-845, the active pharmaceutical ingredient used to formulate Vicinium™ and Proxinium™, and deBouganin, the de-immunized payload used in the company’s systemically-administered drug candidates. [Press release from Eleven Biotherapeutics, Inc. discussing research presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release

Data on Verastem’s Focal Adhesion Kinase Inhibitor Defactinib Presented

Verastem, Inc. announced the oral presentation of data for its lead focal adhesion kinase inhibitor, defactinib, by the company’s scientific collaborator David G. DeNardo, PhD, Assistant Professor of Medicine, Division of Oncology, Department of Immunology, Washington University School of Medicine in St. Louis. [Press release from Verastem, Inc. discussing research presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release

SignalRx to Present on Its First-in-Class Triple PI3K/CDK4-6/BRD4 Inhibitor SRX3177 for Treating Cancer

SignalRx Pharmaceuticals Inc. announced the upcoming presentation of scientific data on the company’s triple PI3K/CDK4-6/BRD4 inhibitor program and first-in-class triple inhibitor SRX3177. [Press release from SignalRx Pharmaceuticals Inc. (PR Newswire Association LLC.) discussing research presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting, Washington, D.C.] Press Release

Cantargia Receives an Intention to Grant Notice in Europe for Its CAN04 Product Candidate

Cantargia AB announced that the company has received an Intention to Grant notice from the European Patent Office for its patent application for the CAN04 product candidate. The patent protects Cantargia’s CAN04 product candidate as a substance as well as its specific use for treatment of various forms of cancer. [Cantargia AB] Press Release

Researchers Named Outstanding Investigators by the National Cancer Institute

Stanford cancer researchers Ronald Levy and Howard Chang have been named Outstanding Investigators by the National Cancer Institute. They were awarded grants of up to $7 million over six years to advance their studies. [Stanford Medicine] Press Release

Brazilian Scientists Reeling as Federal Funds Slashed by Nearly Half

Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US$898 million — a 2.2 billion reais cut from the 5 billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial

Genetic Details of Controversial ‘Three-Parent Baby’ Revealed

When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial

NEW Cell Culture World Congress
May 23-24, 2017
San Diego, United States

NEW GRKs and Arrestins: From Structure to Disease
June 11-16, 2017
Saxtons River, United States

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

NEW Postdoctoral Positions – Epigenetics, Stem Cells and Cancer (University of Copenhagen)

Postdoctoral Fellow – Breast Cancer Stem Cell (University of Kentucky)

Postdoctoral Position – Stem Cell Research (Helmholtz Association)

Postdoctoral Training Fellow – Stem Cell Dynamics in the Adult Hippocampus (The Francis Crick Institute)

Postdoctoral Fellow – Cancer Research (Houston Methodist Research Institute)

Postdoctoral Fellow – Breast Cancer (Tufts University School of Medicine)

Postdoctoral Position – Cancer/Normal Stem Cells (Johns Hopkins University)

Postdoctoral Fellow – Cancer Immunotherapy (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)

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