Volume 2.03 | Jan 23

Cancer Stem Cell News 2.03 January 23, 2013
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TOP STORY
Drug Targets Hard-to-Reach Leukemia Stem Cells Responsible for Relapses
Researchers have discovered that hard-to-reach, drug-resistant leukemia stem cells (LSCs) that overexpress multiple pro-survival protein forms are sensitive, and thus vulnerable, to a novel cancer stem cell-targeting drug currently under development. They found that a compound called sabutoclax appears to selectively target LSCs that express particular protein isoforms through alternatively splicing, a fundamental process in which a gene is able to code for multiple proteins. [Press release from the University of California, San Diego Health System discussing online prepublication in Cell Stem Cell]
Press Release | Abstract | Graphical Abstract

[Free Webinar] ALDH+ Cancer Precursor Cells in Drug Response Prediction - Watch Now.

PUBLICATIONS (Ranked by impact factor of the journal)

BCL-2 Inhibition Targets Oxidative Phosphorylation and Selectively Eradicates Quiescent Human Leukemia Stem Cells
Researchers evaluated mechanisms controlling oxidative state in primary specimens derived from acute myelogenous leukemia patients. Their studies demonstrate three striking findings. First, the majority of functionally defined leukemia stem cells (LSCs) are characterized by relatively low levels of reactive oxygen species (termed ROS-low). Second, ROS-low LSCs aberrantly overexpress BCL-2. Third, BCL-2 inhibition reduced oxidative phosphorylation and selectively eradicated quiescent LSCs. [Cell Stem Cell]
Abstract | Press Release

Tumor-Specific Activation of the c-JUN/MELK Pathway Regulates Glioma Stem Cell Growth in a p53-Dependent Manner
Scientists demonstrated that MELK depletion by shRNA diminishes the growth of glioma stem cell (GSC)-derived mouse intracranial tumors in vivo, induces GFAP (+) glial differentiation of GSCs leading to decreased malignancy of the resulting tumors, and prolongs survival periods of tumor-bearing mice. [Stem Cells] Abstract | Full Article

IGF1 Receptor Signaling Regulates Adaptive Radioprotection in Glioma Stem Cells
Results showed that glioma stem cells (GSCs) evade the damage of repeated radiation not only through innate properties, but also through gradual inducement of resistance pathways and identify the dynamic regulation of GSCs by insulin-like growth factor type 1 (IGF1) receptor signaling as a novel mechanism of adaptive radioprotection. [Stem Cells] Abstract

Chromatin Effector Pygo2 Regulates Mammary Tumor Initiation and Heterogeneity in MMTV-Wnt1 Mice
Results suggest that Pygopus 2 (Pygo2) acts at a step downstream of mammary stem cell accumulation to facilitate transformation, and that it regulates the tumor initiating capacity and lineage preference of the already transformed mammary cells, in MMTV-Wnt1 mice. [Oncogene] Abstract

TLR2 Enhances Ovarian Cancer Stem Cell Self-Renewal and Promotes Tumor Repair and Recurrence
The authors have shown previously that CD44+/MyD88+ epithelial ovarian cancer stem cells are responsible for tumor initiation. In this study, they demonstrated that this population drives tumor repair following surgery- and chemotherapy-induced tumor injury. [Cell Cycle] Abstract

The Cancer Stem Cell Marker CD133 Interacts with Plakoglobin and Controls Desmoglein-2 Protein Levels
Scientists described a cancer stem cell line established from clear cell carcinoma of the ovary (CCC) and show that CD133 interacts with plakoglobin, a desmosomal linker protein. They further demonstrated that knockdown of CD133 by RNA interference results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. [PLoS One] Full Article

Tumor Cells Positive and Negative for the Common Cancer Stem Cell Markers Are Capable of Initiating Tumor Growth and Generating Both Progenies
Investigators showed that tumor cells both positive and negative for the cancer stem cell (CSC) marker (CSC+ and CSC cells, respectively) exhibit similar proliferation in the native states. Using a cell tracing method, they demonstrated that CSC cells exhibit similar tumorigenesis and proliferation as CSC+ cells when they were co-transplanted into immunodeficient mice. Through serial single-cell derived subline construction, the authors further demonstrated that CSC+ and CSC cells from CSC marker expressing tumors could invariably generate both progenies, and their characteristics are maintained among different generations irrespective of the origins. [PLoS One] Full Article

Role of the IL-6-JAK1-STAT3-Oct-4 Pathway in the Conversion of Non-Stem Cancer Cells into Cancer Stem-Like Cells
The authors used cancer stem cell (CSC)-like human breast cancer cells and their alternate subset non-CSCs to investigate how interleukin-6 (IL-6) regulates the conversion of non-CSCs to CSCs. [Cell Signal] Abstract

Leading Malignant Cells Initiate Collective Epithelial Cell Invasion in a Three-Dimensional Heterotypic Tumor Spheroid Model
Researchers found that “invasion-competent” malignant cells induced the collective invasion of otherwise “invasion-incompetent” epithelial cells, and that these two cell types consistently exhibited distinct leader and follower roles during invasion. [Clin Exp Metastasis] Abstract

Prostate Cancer Stem-Like Cells/Cancer-Initiating Cells Have an Autocrine System of Hepatocyte Growth Factor
Researchers found that prostate cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) expressed higher levels of growth factors including hepatocyte growth factor (HGF). The results indicate that HGF secreted by prostate CSCs/CICs and prostate myofibroblasts has a role in the maintenance of prostate CSCs/CICs in an autocrine and paracrine fashion. [Cancer Sci] Abstract

Culture Human Glioma-Derived Tumorspheres with NeuroCult™ - View Publications

REVIEWS
Redox Regulation in Stem-Like Cancer Cells by CD44 Variant Isoforms
Given that cancer cells are often exposed to high levels of reactive oxygen species (ROS) during tumor progression, the ability to avoid the consequences of such exposure is required for cancer cell survival and propagation in vivo. Cancer stem cells, in which defense against ROS is enhanced by CD44 variant isoforms are thus thought to drive tumor growth, chemoresistance and metastasis. [Oncogene] Abstract
INDUSTRY NEWS

Historic $50 Million Gift to Princess Margaret Cancer Centre
Canadian philanthropists Emmanuelle Gattuso, Allan Slaight and the Slaight family made history with a $50 million gift to The Princess Margaret Cancer Foundation. The extraordinary donation is the biggest ever private gift to cancer research in Canadian history and will advance the Princess Margaret Cancer Centre’s Personalized Cancer Medicine initiative. [The Princess Margaret Cancer Foundation] Press Release | Video

Northwestern Medicine Plans $1 Billion Research Investment
Leaders of Northwestern Medicine, comprising Northwestern University Feinberg School of Medicine, Northwestern Medical Faculty Foundation and Northwestern Memorial HealthCare, announced they have made a transformational commitment of more than $1 billion toward creating a leading medical research enterprise on Northwestern’s campus in Chicago’s Streeterville neighborhood. [Northwestern University] Press Release

Verastem Promotes Chief Operating Officer Robert Forrester to President
Verastem, Inc., a clinical-stage biopharmaceutical company focused on discovering and developing drugs to treat cancer by the targeted killing of cancer stem cells, promoted Robert Forrester to President in addition to Chief Operating Officer. [Verastem, Inc.] Press Release

 
POLICY NEWS
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
EVENTS

NEW Global Technology Community: 6th Oncology Biomarkers
March 20-22, 2013
San Francisco, United States

NEW Cold Spring Harbor Laboratory: Cancer Biology & Therapeutics
April 23-27, 2013
Cold Spring Harbor, United States

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

JOB OPPORTUNITIES

Scientist or Engineer – hPSC Bioengineer (STEMCELL Technologies, Inc.)

Postdoctoral Position – Cancer Research (Charite Universitatsmedizin Berlin – MKFZ)

Postdoctoral Fellow – Cancer Biology and Stem Cell (University of Texas at Houston, Medical School)

PhD Student and Postdoctoral Positions – Tumor Immunology and Cancer Stem Cell Research (University Clinics Freiburg)

Postdoctoral Associate (University of California, Berkeley)

Postdoctoral Fellow – Myeloproliferative Neoplasms (Mount Sinai Medical Center)

Postdoctoral Fellow – Stem Cells and Cancer (Tsinghua University)

Postdoctoral Position – Cancer Stem Cell Biology (Spanish National Cancer Research Centre [CNIO])

Postdoctoral Fellow (University of Michigan – Ann Arbor)


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